CA2699892A1 - Pyridyl sulfonamides as modulators of ion channels - Google Patents

Info

Publication number

CA2699892A1

CA2699892A1 CA2699892A CA2699892A CA2699892A1 CA 2699892 A1 CA2699892 A1 CA 2699892A1 CA 2699892 A CA2699892 A CA 2699892A CA 2699892 A CA2699892 A CA 2699892A CA 2699892 A1 CA2699892 A1 CA 2699892A1

Authority

CA

Canada

Prior art keywords

pain

compound according

acute

optionally substituted

ring

Prior art date

2007-09-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 102000004310 Ion Channels Human genes 0.000 title abstract description 5
• -1 Pyridyl sulfonamides Chemical class 0.000 title description 39
• 229940124530 sulfonamide Drugs 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 139
• 239000000203 mixture Substances 0.000 claims abstract description 66
• 238000000034 method Methods 0.000 claims abstract description 53
• 208000002193 Pain Diseases 0.000 claims description 155
• 230000036407 pain Effects 0.000 claims description 115
• 125000001424 substituent group Chemical group 0.000 claims description 57
• 125000001931 aliphatic group Chemical group 0.000 claims description 46
• 208000004296 neuralgia Diseases 0.000 claims description 45
• 230000001154 acute effect Effects 0.000 claims description 34
• 208000021722 neuropathic pain Diseases 0.000 claims description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 230000001684 chronic effect Effects 0.000 claims description 22
• 206010015037 epilepsy Diseases 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 20
• 229920006395 saturated elastomer Polymers 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 17
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
• 208000005298 acute pain Diseases 0.000 claims description 16
• 208000035475 disorder Diseases 0.000 claims description 16
• 208000008035 Back Pain Diseases 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 201000006417 multiple sclerosis Diseases 0.000 claims description 15
• 208000000094 Chronic Pain Diseases 0.000 claims description 14
• 230000002981 neuropathic effect Effects 0.000 claims description 14
• 208000009935 visceral pain Diseases 0.000 claims description 14
• 206010019233 Headaches Diseases 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 206010065390 Inflammatory pain Diseases 0.000 claims description 11
• 208000019695 Migraine disease Diseases 0.000 claims description 11
• 125000001118 alkylidene group Chemical group 0.000 claims description 11
• 206010027599 migraine Diseases 0.000 claims description 11
• 208000006561 Cluster Headache Diseases 0.000 claims description 10
• 208000004404 Intractable Pain Diseases 0.000 claims description 10
• 206010028836 Neck pain Diseases 0.000 claims description 10
• 208000004550 Postoperative Pain Diseases 0.000 claims description 10
• 206010003119 arrhythmia Diseases 0.000 claims description 10
• 125000002619 bicyclic group Chemical group 0.000 claims description 10
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 10
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
• 125000002950 monocyclic group Chemical group 0.000 claims description 10
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
• 206010044652 trigeminal neuralgia Diseases 0.000 claims description 10
• 208000008930 Low Back Pain Diseases 0.000 claims description 9
• 208000016285 Movement disease Diseases 0.000 claims description 9
• 206010061533 Myotonia Diseases 0.000 claims description 9
• 208000000003 Breakthrough pain Diseases 0.000 claims description 8
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 8
• 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 8
• 230000002757 inflammatory effect Effects 0.000 claims description 8
• 208000014674 injury Diseases 0.000 claims description 8
• 201000008482 osteoarthritis Diseases 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 206010002383 Angina Pectoris Diseases 0.000 claims description 7
• 208000019901 Anxiety disease Diseases 0.000 claims description 7
• 206010003591 Ataxia Diseases 0.000 claims description 7
• 206010058019 Cancer Pain Diseases 0.000 claims description 7
• 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 7
• 206010059604 Radicular pain Diseases 0.000 claims description 7
• 208000008765 Sciatica Diseases 0.000 claims description 7
• 230000036506 anxiety Effects 0.000 claims description 7
• 230000006793 arrhythmia Effects 0.000 claims description 7
• 208000006820 Arthralgia Diseases 0.000 claims description 6
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
• 206010021639 Incontinence Diseases 0.000 claims description 6
• 208000007914 Labor Pain Diseases 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 208000013403 hyperactivity Diseases 0.000 claims description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• 208000015706 neuroendocrine disease Diseases 0.000 claims description 6
• 208000020016 psychiatric disease Diseases 0.000 claims description 6
• 239000003981 vehicle Substances 0.000 claims description 6
• 208000005890 Neuroma Diseases 0.000 claims description 5
• 208000001294 Nociceptive Pain Diseases 0.000 claims description 5
• 208000006011 Stroke Diseases 0.000 claims description 5
• 208000027418 Wounds and injury Diseases 0.000 claims description 5
• 230000006378 damage Effects 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
• 208000000450 Pelvic Pain Diseases 0.000 claims description 4
• 206010046543 Urinary incontinence Diseases 0.000 claims description 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 230000003211 malignant effect Effects 0.000 claims description 4
• 208000004998 Abdominal Pain Diseases 0.000 claims description 3
• 208000002485 Adiposis dolorosa Diseases 0.000 claims description 3
• 206010003011 Appendicitis Diseases 0.000 claims description 3
• 208000009137 Behcet syndrome Diseases 0.000 claims description 3
• 206010006002 Bone pain Diseases 0.000 claims description 3
• 206010064012 Central pain syndrome Diseases 0.000 claims description 3
• 206010008479 Chest Pain Diseases 0.000 claims description 3
• 201000009273 Endometriosis Diseases 0.000 claims description 3
• 208000024720 Fabry Disease Diseases 0.000 claims description 3
• 206010016059 Facial pain Diseases 0.000 claims description 3
• 208000001640 Fibromyalgia Diseases 0.000 claims description 3
• 206010019909 Hernia Diseases 0.000 claims description 3
• 208000007514 Herpes zoster Diseases 0.000 claims description 3
• 208000005615 Interstitial Cystitis Diseases 0.000 claims description 3
• 208000035945 Labour pain Diseases 0.000 claims description 3
• 206010024229 Leprosy Diseases 0.000 claims description 3
• 206010028391 Musculoskeletal Pain Diseases 0.000 claims description 3
• 208000030858 Myofascial Pain Syndromes Diseases 0.000 claims description 3
• 206010033645 Pancreatitis Diseases 0.000 claims description 3
• 206010033647 Pancreatitis acute Diseases 0.000 claims description 3
• 208000010886 Peripheral nerve injury Diseases 0.000 claims description 3
• 206010037596 Pyelonephritis Diseases 0.000 claims description 3
• 206010037779 Radiculopathy Diseases 0.000 claims description 3
• 206010038419 Renal colic Diseases 0.000 claims description 3
• 208000000491 Tendinopathy Diseases 0.000 claims description 3
• 206010043255 Tendonitis Diseases 0.000 claims description 3
• 206010043269 Tension headache Diseases 0.000 claims description 3
• 208000008548 Tension-Type Headache Diseases 0.000 claims description 3
• 208000025609 Urogenital disease Diseases 0.000 claims description 3
• 230000003187 abdominal effect Effects 0.000 claims description 3
• 201000003229 acute pancreatitis Diseases 0.000 claims description 3
• 208000034757 axonal type 2FF Charcot-Marie-Tooth disease Diseases 0.000 claims description 3
• 208000029162 bladder disease Diseases 0.000 claims description 3
• 238000002512 chemotherapy Methods 0.000 claims description 3
• 201000001352 cholecystitis Diseases 0.000 claims description 3
• 201000011384 erythromelalgia Diseases 0.000 claims description 3
• 201000000182 femoral cancer Diseases 0.000 claims description 3
• 231100000869 headache Toxicity 0.000 claims description 3
• 208000037584 hereditary sensory and autonomic neuropathy Diseases 0.000 claims description 3
• 208000003243 intestinal obstruction Diseases 0.000 claims description 3
• 210000002414 leg Anatomy 0.000 claims description 3
• 201000001119 neuropathy Diseases 0.000 claims description 3
• 230000007823 neuropathy Effects 0.000 claims description 3
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
• 201000007094 prostatitis Diseases 0.000 claims description 3
• 238000001959 radiotherapy Methods 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• 208000007056 sickle cell anemia Diseases 0.000 claims description 3
• 201000009890 sinusitis Diseases 0.000 claims description 3
• 208000020431 spinal cord injury Diseases 0.000 claims description 3
• 208000005198 spinal stenosis Diseases 0.000 claims description 3
• 208000011580 syndromic disease Diseases 0.000 claims description 3
• 210000001738 temporomandibular joint Anatomy 0.000 claims description 3
• 201000004415 tendinitis Diseases 0.000 claims description 3
• 210000003371 toe Anatomy 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• 208000026533 urinary bladder disease Diseases 0.000 claims description 3
• 201000006474 Brain Ischemia Diseases 0.000 claims description 2
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 206010033557 Palpitations Diseases 0.000 claims description 2
• 208000004983 Phantom Limb Diseases 0.000 claims description 2
• 206010056238 Phantom pain Diseases 0.000 claims description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
• 206010008118 cerebral infarction Diseases 0.000 claims description 2
• 230000005176 gastrointestinal motility Effects 0.000 claims description 2
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• 230000009529 traumatic brain injury Effects 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 13
• 239000003112 inhibitor Substances 0.000 abstract description 9
• DWJMBQYORXLGAE-UHFFFAOYSA-N pyridine-2-sulfonamide Chemical class NS(=O)(=O)C1=CC=CC=N1 DWJMBQYORXLGAE-UHFFFAOYSA-N 0.000 abstract 1
• 239000000243 solution Substances 0.000 description 84
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
• 210000004027 cell Anatomy 0.000 description 33
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
• 125000000217 alkyl group Chemical group 0.000 description 30
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
• 102000018674 Sodium Channels Human genes 0.000 description 28
• 108010052164 Sodium Channels Proteins 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
• 108091006146 Channels Proteins 0.000 description 23
• 235000002639 sodium chloride Nutrition 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• 239000011734 sodium Substances 0.000 description 19
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
• 238000010898 silica gel chromatography Methods 0.000 description 17
• 125000003118 aryl group Chemical group 0.000 description 16
• 210000002569 neuron Anatomy 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• 238000006243 chemical reaction Methods 0.000 description 15
• 239000003814 drug Substances 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• 235000019439 ethyl acetate Nutrition 0.000 description 15
• 230000004044 response Effects 0.000 description 15
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• 238000003556 assay Methods 0.000 description 13
• 201000010099 disease Diseases 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 238000000576 coating method Methods 0.000 description 12
• 210000003594 spinal ganglia Anatomy 0.000 description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• 239000007787 solid Substances 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 239000005557 antagonist Substances 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 230000000638 stimulation Effects 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 10
• 229950010357 tetrodotoxin Drugs 0.000 description 10
• CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 10
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 10
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 239000007995 HEPES buffer Substances 0.000 description 8
• 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 8
• 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 210000004556 brain Anatomy 0.000 description 8
• ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 8
• 210000005036 nerve Anatomy 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 210000001044 sensory neuron Anatomy 0.000 description 8
• VJYNRXFXHKIGLT-UHFFFAOYSA-N 5-[3-(1,3-diethyl-4,6-dioxo-2-sulfanylidene-1,3-diazinan-5-yl)prop-2-enylidene]-1,3-diethyl-2-sulfanylidene-1,3-diazinane-4,6-dione Chemical compound O=C1N(CC)C(=S)N(CC)C(=O)C1C=CC=C1C(=O)N(CC)C(=S)N(CC)C1=O VJYNRXFXHKIGLT-UHFFFAOYSA-N 0.000 description 7
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 108091006629 SLC13A2 Proteins 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 230000035772 mutation Effects 0.000 description 7
• 229920001223 polyethylene glycol Polymers 0.000 description 7
• 229910052708 sodium Inorganic materials 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 241000282414 Homo sapiens Species 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 239000001961 anticonvulsive agent Substances 0.000 description 6
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 229940093499 ethyl acetate Drugs 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 125000001624 naphthyl group Chemical group 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• 230000003287 optical effect Effects 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• UADZSXRKGPSOLT-UHFFFAOYSA-N 6-amino-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C1=NC(N)=CC=C1S(=O)(=O)NC1=NC=CS1 UADZSXRKGPSOLT-UHFFFAOYSA-N 0.000 description 5
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
• 208000004454 Hyperalgesia Diseases 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 238000005481 NMR spectroscopy Methods 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 230000000692 anti-sense effect Effects 0.000 description 5
• 210000003050 axon Anatomy 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
• 239000011248 coating agent Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 239000008103 glucose Substances 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 229920001983 poloxamer Polymers 0.000 description 5
• 229920000642 polymer Polymers 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 239000003195 sodium channel blocking agent Substances 0.000 description 5
• 239000007909 solid dosage form Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 239000001993 wax Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• CCHVCPBBHPRKEI-UHFFFAOYSA-N 6-chloro-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)NC1=NC=CS1 CCHVCPBBHPRKEI-UHFFFAOYSA-N 0.000 description 4
• 239000004215 Carbon black (E152) Substances 0.000 description 4
• 208000002091 Febrile Seizures Diseases 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 208000035154 Hyperesthesia Diseases 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 230000036982 action potential Effects 0.000 description 4
• 235000010443 alginic acid Nutrition 0.000 description 4
• 229920000615 alginic acid Polymers 0.000 description 4
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 4
• 239000012472 biological sample Substances 0.000 description 4
• YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 235000001671 coumarin Nutrition 0.000 description 4
• 229960000956 coumarin Drugs 0.000 description 4
• 125000004093 cyano group Chemical group *C#N 0.000 description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 239000000975 dye Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 238000010304 firing Methods 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 230000002779 inactivation Effects 0.000 description 4
• 239000003701 inert diluent Substances 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 239000002207 metabolite Substances 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 230000003040 nociceptive effect Effects 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 235000019198 oils Nutrition 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 229910001415 sodium ion Inorganic materials 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 239000011593 sulfur Substances 0.000 description 4
• 230000008685 targeting Effects 0.000 description 4
• 238000002560 therapeutic procedure Methods 0.000 description 4
• RCQKXSHSPCBVCC-INIZCTEOSA-N (2s)-2-(4-chloro-5-fluoro-2,3-dihydroindol-1-yl)-4-hydroxy-n-[5-(1,3-thiazol-2-ylsulfamoyl)pyridin-2-yl]butanamide Chemical compound O=C([C@@H](N1C2=C(C(=C(F)C=C2)Cl)CC1)CCO)NC(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 RCQKXSHSPCBVCC-INIZCTEOSA-N 0.000 description 3
• FWIBCWKHNZBDLS-GSVOUGTGSA-N (3r)-3-hydroxyoxolan-2-one Chemical compound O[C@@H]1CCOC1=O FWIBCWKHNZBDLS-GSVOUGTGSA-N 0.000 description 3
• CERKXRDBHIOGGJ-GFCCVEGCSA-N 6-[(3r)-3-hydroxy-2-oxopyrrolidin-1-yl]-n-prop-2-enyl-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound O=C1[C@H](O)CCN1C1=CC=C(S(=O)(=O)N(CC=C)C=2SC=CN=2)C=N1 CERKXRDBHIOGGJ-GFCCVEGCSA-N 0.000 description 3
• QXZKKHONVQGXAK-UHFFFAOYSA-N 6-chloropyridine-3-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=N1 QXZKKHONVQGXAK-UHFFFAOYSA-N 0.000 description 3
• OGPPCINXPHZWCQ-UHFFFAOYSA-N 6-piperazin-1-yl-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C=1C=C(N2CCNCC2)N=CC=1S(=O)(=O)NC1=NC=CS1 OGPPCINXPHZWCQ-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• 241001535291 Analges Species 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 239000012981 Hank's balanced salt solution Substances 0.000 description 3
• 108090000862 Ion Channels Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
• 229910052770 Uranium Inorganic materials 0.000 description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 229940125681 anticonvulsant agent Drugs 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 125000002393 azetidinyl group Chemical group 0.000 description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
• 230000005540 biological transmission Effects 0.000 description 3
• 239000006172 buffering agent Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
• 230000003111 delayed effect Effects 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000006196 drop Substances 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000002883 imidazolyl group Chemical group 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 3
• 125000001786 isothiazolyl group Chemical group 0.000 description 3
• 125000000842 isoxazolyl group Chemical group 0.000 description 3
• 229960001848 lamotrigine Drugs 0.000 description 3
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 3
• 229960004194 lidocaine Drugs 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 230000028161 membrane depolarization Effects 0.000 description 3
• 238000002779 membrane potential assay Methods 0.000 description 3
• 125000002757 morpholinyl group Chemical group 0.000 description 3
• 210000003205 muscle Anatomy 0.000 description 3
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 3
• 230000001537 neural effect Effects 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 description 3
• 125000002971 oxazolyl group Chemical group 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 229910052698 phosphorus Inorganic materials 0.000 description 3
• 239000011574 phosphorus Substances 0.000 description 3
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 3
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
• 125000003373 pyrazinyl group Chemical group 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000008247 solid mixture Substances 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 3
• 229960002372 tetracaine Drugs 0.000 description 3
• GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 125000004306 triazinyl group Chemical group 0.000 description 3
• 125000001425 triazolyl group Chemical group 0.000 description 3
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 3
• 210000000427 trigeminal ganglion Anatomy 0.000 description 3
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• RUVUQFUJOWNEBJ-JTQLQIEISA-N (3s)-3-(4-chloro-5-fluoro-2,3-dihydroindol-1-yl)oxolan-2-one Chemical compound C1CC2=C(Cl)C(F)=CC=C2N1[C@H]1CCOC1=O RUVUQFUJOWNEBJ-JTQLQIEISA-N 0.000 description 2
• VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
• XEBPDGUUAHUFKA-INIZCTEOSA-N 6-[(3s)-3-(4-chloro-5-fluoro-2,3-dihydroindol-1-yl)-2-oxopyrrolidin-1-yl]-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C([C@@H](C1=O)N2C3=CC=C(C(=C3CC2)Cl)F)CN1C(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 XEBPDGUUAHUFKA-INIZCTEOSA-N 0.000 description 2
• SVVZCUGMEADYQO-SFHVURJKSA-N 6-[(3s)-3-(6-chloro-3,4-dihydro-2h-quinolin-1-yl)-2-oxopyrrolidin-1-yl]-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C([C@@H](C1=O)N2C3=CC=C(C=C3CCC2)Cl)CN1C(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 SVVZCUGMEADYQO-SFHVURJKSA-N 0.000 description 2
• QYICGRCILWJCBR-NRFANRHFSA-N 6-[(3s)-3-(6-chloro-3,4-dihydro-2h-quinolin-1-yl)-2-oxopyrrolidin-1-yl]-n-prop-2-enyl-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound C([C@@H](C1=O)N2C3=CC=C(C=C3CCC2)Cl)CN1C(N=C1)=CC=C1S(=O)(=O)N(CC=C)C1=NC=CS1 QYICGRCILWJCBR-NRFANRHFSA-N 0.000 description 2
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 206010001497 Agitation Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 101150041968 CDC13 gene Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 229910002651 NO3 Inorganic materials 0.000 description 2
• 208000028389 Nerve injury Diseases 0.000 description 2
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 210000003766 afferent neuron Anatomy 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 230000000202 analgesic effect Effects 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 239000005441 aurora Substances 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• HJZVHUQSQGITAM-UHFFFAOYSA-N butanamide Chemical compound CC[CH]C(N)=O HJZVHUQSQGITAM-UHFFFAOYSA-N 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 229960002504 capsaicin Drugs 0.000 description 2
• 235000017663 capsaicin Nutrition 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 210000005056 cell body Anatomy 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000007405 data analysis Methods 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000006735 deficit Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
• 229940043264 dodecyl sulfate Drugs 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 230000007831 electrophysiology Effects 0.000 description 2
• 238000002001 electrophysiology Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 238000009505 enteric coating Methods 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 229940050410 gluconate Drugs 0.000 description 2
• 150000002334 glycols Chemical class 0.000 description 2
• 230000002055 immunohistochemical effect Effects 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 150000002596 lactones Chemical class 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 238000011068 loading method Methods 0.000 description 2
• 229960005015 local anesthetics Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 238000007726 management method Methods 0.000 description 2
• QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 2
• 239000004530 micro-emulsion Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 230000008764 nerve damage Effects 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 230000000955 neuroendocrine Effects 0.000 description 2
• 210000000929 nociceptor Anatomy 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 239000002831 pharmacologic agent Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 230000036390 resting membrane potential Effects 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 230000020341 sensory perception of pain Effects 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 229910052710 silicon Inorganic materials 0.000 description 2
• 239000010703 silicon Substances 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 210000000278 spinal cord Anatomy 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 230000002459 sustained effect Effects 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 125000004001 thioalkyl group Chemical group 0.000 description 2
• 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• MEZHHUMSKXFEOU-SSDOTTSWSA-N (2r)-2-(4-fluoroindol-1-yl)propanoic acid Chemical compound C1=CC=C2N([C@@H](C(O)=O)C)C=CC2=C1F MEZHHUMSKXFEOU-SSDOTTSWSA-N 0.000 description 1
• JCFFIYNDTBBSOU-SSDOTTSWSA-N (2r)-2-(6-chloroindol-1-yl)propanoic acid Chemical compound C1=C(Cl)C=C2N([C@@H](C(O)=O)C)C=CC2=C1 JCFFIYNDTBBSOU-SSDOTTSWSA-N 0.000 description 1
• DCUZXIQWXSLMKN-XMMPIXPASA-N (2r)-2-[tert-butyl(diphenyl)silyl]oxy-4-hydroxy-n-[5-(1,3-thiazol-2-ylsulfamoyl)pyridin-2-yl]butanamide Chemical compound O=C([C@@H](CCO)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 DCUZXIQWXSLMKN-XMMPIXPASA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
• FGDFCPQKZXVVEX-GOSISDBHSA-N (3r)-3-[tert-butyl(diphenyl)silyl]oxyoxolan-2-one Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)O[C@@H]1CCOC1=O FGDFCPQKZXVVEX-GOSISDBHSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• WNTGYJSOUMFZEP-SSDOTTSWSA-N (R)-mecoprop Chemical compound OC(=O)[C@@H](C)OC1=CC=C(Cl)C=C1C WNTGYJSOUMFZEP-SSDOTTSWSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
• LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical class NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 1
• ZGDMHRLSOGHDSZ-UHFFFAOYSA-N 4-chloro-5-fluoro-2,3-dihydro-1h-indole Chemical compound FC1=CC=C2NCCC2=C1Cl ZGDMHRLSOGHDSZ-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
• USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
• AKVNZBVRZWUMIE-MRXNPFEDSA-N 6-[4-[(2r)-2-(4-chloro-2-methylphenoxy)propanoyl]piperazin-1-yl]-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound O([C@H](C)C(=O)N1CCN(CC1)C=1N=CC(=CC=1)S(=O)(=O)NC=1SC=CN=1)C1=CC=C(Cl)C=C1C AKVNZBVRZWUMIE-MRXNPFEDSA-N 0.000 description 1
• WBUAMSQPLILAHT-MRXNPFEDSA-N 6-[4-[(2r)-2-(4-fluoroindol-1-yl)propanoyl]piperazin-1-yl]-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound O=C([C@@H](C)N1C2=CC=CC(F)=C2C=C1)N(CC1)CCN1C(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 WBUAMSQPLILAHT-MRXNPFEDSA-N 0.000 description 1
• YSEVEARMNQKPCU-MRXNPFEDSA-N 6-[4-[(2r)-2-(6-chloroindol-1-yl)propanoyl]piperazin-1-yl]-n-(1,3-thiazol-2-yl)pyridine-3-sulfonamide Chemical compound O=C([C@@H](C)N1C2=CC(Cl)=CC=C2C=C1)N(CC1)CCN1C(N=C1)=CC=C1S(=O)(=O)NC1=NC=CS1 YSEVEARMNQKPCU-MRXNPFEDSA-N 0.000 description 1
• PASUADIMFGAUDB-UHFFFAOYSA-N 6-chloro-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(Cl)=CC=C21 PASUADIMFGAUDB-UHFFFAOYSA-N 0.000 description 1
• QAJYCQZQLVENRZ-UHFFFAOYSA-N 6-chloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1 QAJYCQZQLVENRZ-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000031976 Channelopathies Diseases 0.000 description 1
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 239000007836 KH2PO4 Substances 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
• XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000019022 Mood disease Diseases 0.000 description 1
• 208000012905 Myotonic disease Diseases 0.000 description 1
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• 102000004194 NAV1.8 Voltage-Gated Sodium Channel Human genes 0.000 description 1
• 108010056565 NAV1.8 Voltage-Gated Sodium Channel Proteins 0.000 description 1
• BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• JQGGAELIYHNDQS-UHFFFAOYSA-N Nic 12 Natural products CC(C=CC(=O)C)c1ccc2C3C4OC4C5(O)CC=CC(=O)C5(C)C3CCc2c1 JQGGAELIYHNDQS-UHFFFAOYSA-N 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 101000870363 Oryctolagus cuniculus Glutathione S-transferase Yc Proteins 0.000 description 1
• BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
• UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
• 206010061334 Partial seizures Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 206010061339 Perineal pain Diseases 0.000 description 1
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 206010039897 Sedation Diseases 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 206010042674 Swelling Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 208000026802 afebrile Diseases 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 206010053552 allodynia Diseases 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003868 ammonium compounds Chemical class 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000000330 anaesthesiologic effect Effects 0.000 description 1
• 230000036592 analgesia Effects 0.000 description 1
• 229940035674 anesthetics Drugs 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940111136 antiinflammatory and antirheumatic drug fenamates Drugs 0.000 description 1
• 229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 125000005228 aryl sulfonate group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 239000005388 borosilicate glass Substances 0.000 description 1
• 229960003150 bupivacaine Drugs 0.000 description 1
• RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
• 229960001736 buprenorphine Drugs 0.000 description 1
• DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
• IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 description 1
• 229960001113 butorphanol Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 229960000623 carbamazepine Drugs 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 239000000679 carrageenan Substances 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 229940113118 carrageenan Drugs 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 229910052729 chemical element Inorganic materials 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 208000018912 cluster headache syndrome Diseases 0.000 description 1
• 229960004126 codeine Drugs 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000010835 comparative analysis Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000012050 conventional carrier Substances 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000002999 depolarising effect Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
• 229960004193 dextropropoxyphene Drugs 0.000 description 1
• VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 description 1
• 229960003461 dezocine Drugs 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
• 229960000616 diflunisal Drugs 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
• 229960002986 dinoprostone Drugs 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003221 ear drop Substances 0.000 description 1
• 229940047652 ear drops Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 230000008519 endogenous mechanism Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 239000005038 ethylene vinyl acetate Substances 0.000 description 1
• XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
• 229960005293 etodolac Drugs 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 229960001419 fenoprofen Drugs 0.000 description 1
• 229960002428 fentanyl Drugs 0.000 description 1
• IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 229960002390 flurbiprofen Drugs 0.000 description 1
• SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
• 230000004907 flux Effects 0.000 description 1
• 238000003209 gene knockout Methods 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 230000036433 growing body Effects 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000004475 heteroaralkyl group Chemical group 0.000 description 1
• 125000005114 heteroarylalkoxy group Chemical group 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
• 229960001410 hydromorphone Drugs 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 238000003365 immunocytochemistry Methods 0.000 description 1
• 238000007901 in situ hybridization Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 150000002475 indoles Chemical class 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000002780 ion channel assay Methods 0.000 description 1
• 229940126181 ion channel inhibitor Drugs 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
• 229960000991 ketoprofen Drugs 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229960003406 levorphanol Drugs 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 229960003803 meclofenamic acid Drugs 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229960003464 mefenamic acid Drugs 0.000 description 1
• 230000025350 membrane depolarization involved in regulation of action potential Effects 0.000 description 1
• 229960001797 methadone Drugs 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• VLPIATFUUWWMKC-UHFFFAOYSA-N mexiletine Chemical compound CC(N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-UHFFFAOYSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 230000004784 molecular pathogenesis Effects 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 235000019796 monopotassium phosphate Nutrition 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
• 230000000869 mutational effect Effects 0.000 description 1
• 210000000107 myocyte Anatomy 0.000 description 1
• 208000029264 myotonic syndrome Diseases 0.000 description 1
• 229960004270 nabumetone Drugs 0.000 description 1
• NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
• 229960000805 nalbuphine Drugs 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
• 229960003940 naproxen sodium Drugs 0.000 description 1
• 230000003533 narcotic effect Effects 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 210000001640 nerve ending Anatomy 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 210000004412 neuroendocrine cell Anatomy 0.000 description 1
• 230000008587 neuronal excitability Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 108091008700 nociceptors Proteins 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 229940121367 non-opioid analgesics Drugs 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 229940041678 oral spray Drugs 0.000 description 1
• 239000000668 oral spray Substances 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
• 229960002739 oxaprozin Drugs 0.000 description 1
• 229960002085 oxycodone Drugs 0.000 description 1
• 229960005118 oxymorphone Drugs 0.000 description 1
• 230000008052 pain pathway Effects 0.000 description 1
• 230000008058 pain sensation Effects 0.000 description 1
• 229960005489 paracetamol Drugs 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 238000012402 patch clamp technique Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
• 229960005301 pentazocine Drugs 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 229960000482 pethidine Drugs 0.000 description 1
• 238000001050 pharmacotherapy Methods 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 229960002895 phenylbutazone Drugs 0.000 description 1
• VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 238000000554 physical therapy Methods 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 229960002702 piroxicam Drugs 0.000 description 1
• QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 229920001992 poloxamer 407 Polymers 0.000 description 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 239000004632 polycaprolactone Substances 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• UNYWISZSMFIKJI-UHFFFAOYSA-N prop-2-ene-1-sulfonamide Chemical compound NS(=O)(=O)CC=C UNYWISZSMFIKJI-UHFFFAOYSA-N 0.000 description 1
• 150000004672 propanoic acids Chemical class 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 210000000449 purkinje cell Anatomy 0.000 description 1
• 150000003217 pyrazoles Chemical class 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 1
• RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000036280 sedation Effects 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 150000003385 sodium Chemical class 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 229960000894 sulindac Drugs 0.000 description 1
• MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 210000001138 tear Anatomy 0.000 description 1
• MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
• 239000012085 test solution Substances 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 230000010989 thermoception Effects 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 208000037816 tissue injury Diseases 0.000 description 1
• 229960001017 tolmetin Drugs 0.000 description 1
• UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000002646 transcutaneous electrical nerve stimulation Methods 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• FQCQGOZEWWPOKI-UHFFFAOYSA-K trisalicylate-choline Chemical compound [Mg+2].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O FQCQGOZEWWPOKI-UHFFFAOYSA-K 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 125000005500 uronium group Chemical group 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 1
• 102000008538 voltage-gated sodium channel activity proteins Human genes 0.000 description 1
• 108040002416 voltage-gated sodium channel activity proteins Proteins 0.000 description 1
• 238000003260 vortexing Methods 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1