CA3118913C - Compositions and methods for transmucosal absorption - Google Patents

Info

Publication number

CA3118913C

CA3118913C CA3118913A CA3118913A CA3118913C CA 3118913 C CA3118913 C CA 3118913C CA 3118913 A CA3118913 A CA 3118913A CA 3118913 A CA3118913 A CA 3118913A CA 3118913 C CA3118913 C CA 3118913C

Authority

CA

Canada

Prior art keywords

equal

administration

hours

composition

cyclobenzaprine

Prior art date

2012-06-15

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.)

Active

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000000203 mixture Substances 0.000 title claims abstract description 580
• 238000010521 absorption reaction Methods 0.000 title claims abstract description 249
• 238000000034 method Methods 0.000 title abstract description 211
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 claims abstract description 274
• 239000002610 basifying agent Substances 0.000 claims abstract description 94
• 208000001640 Fibromyalgia Diseases 0.000 claims abstract description 45
• 229960000836 amitriptyline Drugs 0.000 claims description 265
• 238000009472 formulation Methods 0.000 claims description 131
• 239000000243 solution Substances 0.000 claims description 131
• 230000036470 plasma concentration Effects 0.000 claims description 129
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 58
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 43
• 230000007958 sleep Effects 0.000 claims description 43
• 208000019116 sleep disease Diseases 0.000 claims description 40
• 238000011282 treatment Methods 0.000 claims description 40
• 208000024891 symptom Diseases 0.000 claims description 39
• 235000019796 monopotassium phosphate Nutrition 0.000 claims description 36
• 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 32
• 239000000843 powder Substances 0.000 claims description 29
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 24
• 230000000472 traumatic effect Effects 0.000 claims description 22
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 18
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 17
• 239000007921 spray Substances 0.000 claims description 17
• 208000002193 Pain Diseases 0.000 claims description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 16
• 239000006190 sub-lingual tablet Substances 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 14
• 235000019799 monosodium phosphate Nutrition 0.000 claims description 14
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 14
• 208000020685 sleep-wake disease Diseases 0.000 claims description 14
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 14
• 208000019901 Anxiety disease Diseases 0.000 claims description 13
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 13
• 230000009529 traumatic brain injury Effects 0.000 claims description 13
• 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 12
• PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 12
• 229910000029 sodium carbonate Inorganic materials 0.000 claims description 12
• 235000017550 sodium carbonate Nutrition 0.000 claims description 12
• 239000001488 sodium phosphate Substances 0.000 claims description 12
• 229940098466 sublingual tablet Drugs 0.000 claims description 12
• 238000011161 development Methods 0.000 claims description 10
• 239000001508 potassium citrate Substances 0.000 claims description 10
• QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 10
• 239000001509 sodium citrate Substances 0.000 claims description 10
• 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 10
• 235000019798 tripotassium phosphate Nutrition 0.000 claims description 10
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 10
• 229910000406 trisodium phosphate Inorganic materials 0.000 claims description 10
• 235000019801 trisodium phosphate Nutrition 0.000 claims description 10
• 229910000019 calcium carbonate Inorganic materials 0.000 claims description 9
• 235000010216 calcium carbonate Nutrition 0.000 claims description 9
• 235000015870 tripotassium citrate Nutrition 0.000 claims description 9
• HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 9
• 235000019263 trisodium citrate Nutrition 0.000 claims description 9
• 229940038773 trisodium citrate Drugs 0.000 claims description 9
• 208000007101 Muscle Cramp Diseases 0.000 claims description 8
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 8
• 208000005392 Spasm Diseases 0.000 claims description 8
• 238000007596 consolidation process Methods 0.000 claims description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 claims description 8
• 235000011181 potassium carbonates Nutrition 0.000 claims description 8
• 208000000094 Chronic Pain Diseases 0.000 claims description 7
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
• 239000007983 Tris buffer Substances 0.000 claims description 7
• 239000006189 buccal tablet Substances 0.000 claims description 7
• NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 7
• 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 7
• UZLGHNUASUZUOR-UHFFFAOYSA-L dipotassium;3-carboxy-3-hydroxypentanedioate Chemical compound [K+].[K+].OC(=O)CC(O)(C([O-])=O)CC([O-])=O UZLGHNUASUZUOR-UHFFFAOYSA-L 0.000 claims description 7
• 230000000977 initiatory effect Effects 0.000 claims description 7
• 239000007937 lozenge Substances 0.000 claims description 7
• 235000011056 potassium acetate Nutrition 0.000 claims description 7
• 239000011736 potassium bicarbonate Substances 0.000 claims description 7
• 235000015497 potassium bicarbonate Nutrition 0.000 claims description 7
• 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 7
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 7
• 239000001632 sodium acetate Substances 0.000 claims description 7
• 235000017281 sodium acetate Nutrition 0.000 claims description 7
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 7
• 229940046011 buccal tablet Drugs 0.000 claims description 6
• 239000002526 disodium citrate Substances 0.000 claims description 6
• 235000019262 disodium citrate Nutrition 0.000 claims description 6
• CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 claims description 6
• 150000001875 compounds Chemical class 0.000 abstract description 75
• 239000003814 drug Substances 0.000 abstract description 51
• 230000001225 therapeutic effect Effects 0.000 abstract description 13
• 230000008901 benefit Effects 0.000 abstract description 6
• 229940124597 therapeutic agent Drugs 0.000 abstract description 2
• JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 811
• 229960003572 cyclobenzaprine Drugs 0.000 description 806
• 241000282472 Canis lupus familiaris Species 0.000 description 128
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
• 239000003826 tablet Substances 0.000 description 92
• XECQQDXTQRYYBH-UHFFFAOYSA-N 3-(11-dibenzo[1,2-a:1',2'-e][7]annulenylidene)-N-methyl-1-propanamine Chemical compound C1=CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 XECQQDXTQRYYBH-UHFFFAOYSA-N 0.000 description 84
• 239000002904 solvent Substances 0.000 description 53
• 235000019797 dipotassium phosphate Nutrition 0.000 description 43
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 43
• 229940079593 drug Drugs 0.000 description 42
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• 239000012535 impurity Substances 0.000 description 39
• 230000000694 effects Effects 0.000 description 38
• 239000000523 sample Substances 0.000 description 38
• 230000002354 daily effect Effects 0.000 description 35
• 102000005962 receptors Human genes 0.000 description 35
• 108020003175 receptors Proteins 0.000 description 35
• 238000012360 testing method Methods 0.000 description 35
• 238000004458 analytical method Methods 0.000 description 33
• 229960004134 propofol Drugs 0.000 description 33
• OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 33
• 239000012071 phase Substances 0.000 description 31
• 210000004369 blood Anatomy 0.000 description 29
• 239000008280 blood Substances 0.000 description 29
• PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 27
• 230000027455 binding Effects 0.000 description 27
• 239000007884 disintegrant Substances 0.000 description 27
• 229960001158 nortriptyline Drugs 0.000 description 27
• 239000003795 chemical substances by application Substances 0.000 description 26
• 238000003556 assay Methods 0.000 description 24
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 24
• 238000003908 quality control method Methods 0.000 description 23
• 229910019142 PO4 Inorganic materials 0.000 description 21
• 238000001990 intravenous administration Methods 0.000 description 21
• 239000010452 phosphate Substances 0.000 description 21
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 21
• 150000003839 salts Chemical class 0.000 description 21
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
• 230000007423 decrease Effects 0.000 description 20
• 241001465754 Metazoa Species 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• 239000007836 KH2PO4 Substances 0.000 description 18
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 18
• 210000002700 urine Anatomy 0.000 description 18
• 230000014759 maintenance of location Effects 0.000 description 17
• 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 16
• 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 16
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 16
• 239000000314 lubricant Substances 0.000 description 16
• LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 15
• 230000009286 beneficial effect Effects 0.000 description 15
• 238000002347 injection Methods 0.000 description 15
• 239000007924 injection Substances 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 210000002105 tongue Anatomy 0.000 description 15
• -1 (10,11-dihydro-5H-dibenzo [a,d] cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine Chemical compound 0.000 description 14
• 241000282412 Homo Species 0.000 description 14
• 238000002474 experimental method Methods 0.000 description 14
• 239000002207 metabolite Substances 0.000 description 14
• 230000036961 partial effect Effects 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 239000000126 substance Substances 0.000 description 14
• 239000007864 aqueous solution Substances 0.000 description 13
• 210000003169 central nervous system Anatomy 0.000 description 13
• 239000004615 ingredient Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 239000007935 oral tablet Substances 0.000 description 12
• 239000000546 pharmaceutical excipient Substances 0.000 description 12
• 208000022925 sleep disturbance Diseases 0.000 description 12
• 239000005557 antagonist Substances 0.000 description 11
• 238000011088 calibration curve Methods 0.000 description 11
• 230000001684 chronic effect Effects 0.000 description 11
• 206010016256 fatigue Diseases 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 238000009826 distribution Methods 0.000 description 10
• 238000011002 quantification Methods 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 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 9
• 229930195725 Mannitol Natural products 0.000 description 9
• 239000004067 bulking agent Substances 0.000 description 9
• 229960000913 crospovidone Drugs 0.000 description 9
• 230000003247 decreasing effect Effects 0.000 description 9
• 230000018109 developmental process Effects 0.000 description 9
• 235000003599 food sweetener Nutrition 0.000 description 9
• 235000010355 mannitol Nutrition 0.000 description 9
• 239000000594 mannitol Substances 0.000 description 9
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 9
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 235000015424 sodium Nutrition 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 229940083542 sodium Drugs 0.000 description 9
• 239000003765 sweetening agent Substances 0.000 description 9
• 208000011580 syndromic disease Diseases 0.000 description 9
• 235000014755 Eruca sativa Nutrition 0.000 description 8
• 244000024675 Eruca sativa Species 0.000 description 8
• 229920002472 Starch Polymers 0.000 description 8
• 230000001800 adrenalinergic effect Effects 0.000 description 8
• 238000004364 calculation method Methods 0.000 description 8
• 239000008119 colloidal silica Substances 0.000 description 8
• 230000006378 damage Effects 0.000 description 8
• 239000000796 flavoring agent Substances 0.000 description 8
• 235000019634 flavors Nutrition 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 210000004379 membrane Anatomy 0.000 description 8
• 239000012528 membrane Substances 0.000 description 8
• 238000002552 multiple reaction monitoring Methods 0.000 description 8
• 235000019698 starch Nutrition 0.000 description 8
• 238000002560 therapeutic procedure Methods 0.000 description 8
• 229940116892 5 Hydroxytryptamine 2B receptor antagonist Drugs 0.000 description 7
• 102100024956 5-hydroxytryptamine receptor 2B Human genes 0.000 description 7
• 101710138092 5-hydroxytryptamine receptor 2B Proteins 0.000 description 7
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 7
• 206010041349 Somnolence Diseases 0.000 description 7
• 238000009825 accumulation Methods 0.000 description 7
• 230000002411 adverse Effects 0.000 description 7
• 239000003086 colorant Substances 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 239000012458 free base Substances 0.000 description 7
• 239000007789 gas Substances 0.000 description 7
• 208000014674 injury Diseases 0.000 description 7
• 238000002156 mixing Methods 0.000 description 7
• 230000036407 pain Effects 0.000 description 7
• 238000012216 screening Methods 0.000 description 7
• 239000008107 starch Substances 0.000 description 7
• 229940032147 starch Drugs 0.000 description 7
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
• 238000012546 transfer Methods 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• 229910002016 Aerosil® 200 Inorganic materials 0.000 description 6
• 206010002091 Anaesthesia Diseases 0.000 description 6
• 229920003085 Kollidon® CL Polymers 0.000 description 6
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
• 239000002033 PVDF binder Substances 0.000 description 6
• 208000027418 Wounds and injury Diseases 0.000 description 6
• 240000008042 Zea mays Species 0.000 description 6
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 230000037005 anaesthesia Effects 0.000 description 6
• 238000013103 analytical ultracentrifugation Methods 0.000 description 6
• 230000036506 anxiety Effects 0.000 description 6
• 230000034994 death Effects 0.000 description 6
• 229910000397 disodium phosphate Inorganic materials 0.000 description 6
• 235000019800 disodium phosphate Nutrition 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 206010022437 insomnia Diseases 0.000 description 6
• 229910052744 lithium Inorganic materials 0.000 description 6
• 210000004185 liver Anatomy 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 238000002483 medication Methods 0.000 description 6
• 230000004060 metabolic process Effects 0.000 description 6
• 210000004877 mucosa Anatomy 0.000 description 6
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 6
• 230000002685 pulmonary effect Effects 0.000 description 6
• 210000003296 saliva Anatomy 0.000 description 6
• 230000002618 waking effect Effects 0.000 description 6
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 5
• 239000000120 Artificial Saliva Substances 0.000 description 5
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 5
• 206010013980 Dyssomnias Diseases 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 239000012496 blank sample Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 238000013461 design Methods 0.000 description 5
• 238000004090 dissolution Methods 0.000 description 5
• 229960001340 histamine Drugs 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000010354 integration Effects 0.000 description 5
• 238000011835 investigation Methods 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 5
• 238000000622 liquid--liquid extraction Methods 0.000 description 5
• 235000009973 maize Nutrition 0.000 description 5
• 239000007922 nasal spray Substances 0.000 description 5
• 229940096978 oral tablet Drugs 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 239000012487 rinsing solution Substances 0.000 description 5
• 229940076279 serotonin Drugs 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 238000000638 solvent extraction Methods 0.000 description 5
• 238000004885 tandem mass spectrometry Methods 0.000 description 5
• 238000012549 training Methods 0.000 description 5
• 230000009898 traumatic memory Effects 0.000 description 5
• 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 4
• 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• 108010078791 Carrier Proteins Proteins 0.000 description 4
• 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 4
• 229920002261 Corn starch Polymers 0.000 description 4
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
• 101710133325 Eukaryotic translation initiation factor NCBP Proteins 0.000 description 4
• 108091006027 G proteins Proteins 0.000 description 4
• 102000030782 GTP binding Human genes 0.000 description 4
• 108091000058 GTP-Binding Proteins 0.000 description 4
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 101150104779 HTR2A gene Proteins 0.000 description 4
• 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 4
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
• 206010029412 Nightmare Diseases 0.000 description 4
• 239000004743 Polypropylene Substances 0.000 description 4
• 208000022249 Sleep-Wake Transition disease Diseases 0.000 description 4
• 208000032140 Sleepiness Diseases 0.000 description 4
• 239000008186 active pharmaceutical agent Substances 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
• 239000011575 calcium Substances 0.000 description 4
• VXEAYBOGHINOKW-UHFFFAOYSA-N cyclobenzaprine hydrochloride Chemical compound Cl.C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 VXEAYBOGHINOKW-UHFFFAOYSA-N 0.000 description 4
• 208000017004 dementia pugilistica Diseases 0.000 description 4
• 238000010520 demethylation reaction Methods 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 230000037406 food intake Effects 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000009533 lab test Methods 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 230000015654 memory Effects 0.000 description 4
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
• 239000008108 microcrystalline cellulose Substances 0.000 description 4
• 229940016286 microcrystalline cellulose Drugs 0.000 description 4
• 229940111688 monobasic potassium phosphate Drugs 0.000 description 4
• 229940097496 nasal spray Drugs 0.000 description 4
• 238000001139 pH measurement Methods 0.000 description 4
• 229920001155 polypropylene Polymers 0.000 description 4
• 238000005070 sampling Methods 0.000 description 4
• 230000019491 signal transduction Effects 0.000 description 4
• 239000002002 slurry Substances 0.000 description 4
• 238000012421 spiking Methods 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 238000010200 validation analysis Methods 0.000 description 4
• 239000011800 void material Substances 0.000 description 4
• 102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 3
• 101710138093 5-hydroxytryptamine receptor 2C Proteins 0.000 description 3
• KFYRPLNVJVHZGT-UHFFFAOYSA-N Amitriptyline hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KFYRPLNVJVHZGT-UHFFFAOYSA-N 0.000 description 3
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• 208000020401 Depressive disease Diseases 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• 206010016754 Flashback Diseases 0.000 description 3
• 101000939535 Homo sapiens UDP-glucuronosyltransferase 2B10 Proteins 0.000 description 3
• 235000019759 Maize starch Nutrition 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 102000011923 Thyrotropin Human genes 0.000 description 3
• 108010061174 Thyrotropin Proteins 0.000 description 3
• 102100029161 UDP-glucuronosyltransferase 1A4 Human genes 0.000 description 3
• 101710205490 UDP-glucuronosyltransferase 1A4 Proteins 0.000 description 3
• 102100029634 UDP-glucuronosyltransferase 2B10 Human genes 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 238000000540 analysis of variance Methods 0.000 description 3
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 239000012472 biological sample Substances 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 150000001720 carbohydrates Chemical class 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• 208000010877 cognitive disease Diseases 0.000 description 3
• 229960000500 cyclobenzaprine hydrochloride Drugs 0.000 description 3
• 230000017858 demethylation Effects 0.000 description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
• 229960003638 dopamine Drugs 0.000 description 3
• 238000001647 drug administration Methods 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 230000002255 enzymatic effect Effects 0.000 description 3
• VJYFKVYYMZPMAB-UHFFFAOYSA-N ethoprophos Chemical compound CCCSP(=O)(OCC)SCCC VJYFKVYYMZPMAB-UHFFFAOYSA-N 0.000 description 3
• 238000011156 evaluation Methods 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 230000003834 intracellular effect Effects 0.000 description 3
• BQDBKDMTIJBJLA-UHFFFAOYSA-N metopimazine Chemical compound C12=CC(S(=O)(=O)C)=CC=C2SC2=CC=CC=C2N1CCCN1CCC(C(N)=O)CC1 BQDBKDMTIJBJLA-UHFFFAOYSA-N 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 238000012544 monitoring process Methods 0.000 description 3
• 230000003551 muscarinic effect Effects 0.000 description 3
• 238000001543 one-way ANOVA Methods 0.000 description 3
• 238000009597 pregnancy test Methods 0.000 description 3
• 239000008213 purified water Substances 0.000 description 3
• 230000003252 repetitive effect Effects 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 229920003109 sodium starch glycolate Polymers 0.000 description 3
• 239000008109 sodium starch glycolate Substances 0.000 description 3
• 229940079832 sodium starch glycolate Drugs 0.000 description 3
• 235000010356 sorbitol Nutrition 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 239000012086 standard solution Substances 0.000 description 3
• 210000002784 stomach Anatomy 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 150000005846 sugar alcohols Chemical class 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 2
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-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
• 102000017910 Adrenergic receptor Human genes 0.000 description 2
• 108010088751 Albumins Proteins 0.000 description 2
• 102000009027 Albumins Human genes 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 102000017926 CHRM2 Human genes 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
• 101150012960 Chrm2 gene Proteins 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 2
• DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
• SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
• 229930091371 Fructose Natural products 0.000 description 2
• 239000005715 Fructose Substances 0.000 description 2
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
• 208000005176 Hepatitis C Diseases 0.000 description 2
• 102000000543 Histamine Receptors Human genes 0.000 description 2
• 108010002059 Histamine Receptors Proteins 0.000 description 2
• 101150013372 Htr2c gene Proteins 0.000 description 2
• 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 2
• 208000005615 Interstitial Cystitis Diseases 0.000 description 2
• 208000015814 Intrinsic Sleep disease Diseases 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical compound CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 239000004367 Lipase Substances 0.000 description 2
• 102000004882 Lipase Human genes 0.000 description 2
• 108090001060 Lipase Proteins 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 102000007207 Muscarinic M1 Receptor Human genes 0.000 description 2
• 108010008406 Muscarinic M1 Receptor Proteins 0.000 description 2
• 208000000224 Night Terrors Diseases 0.000 description 2
• 101150053185 P450 gene Proteins 0.000 description 2
• DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
• 206010062519 Poor quality sleep Diseases 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 241000219061 Rheum Species 0.000 description 2
• 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 2
• 208000010340 Sleep Deprivation Diseases 0.000 description 2
• 206010041347 Somnambulism Diseases 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 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 2
• 229940123445 Tricyclic antidepressant Drugs 0.000 description 2
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
• MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000000674 adrenergic antagonist Substances 0.000 description 2
• 229960005119 amitriptyline hydrochloride Drugs 0.000 description 2
• 229940035676 analgesics Drugs 0.000 description 2
• 239000000730 antalgic agent Substances 0.000 description 2
• 239000001961 anticonvulsive agent Substances 0.000 description 2
• PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 238000010241 blood sampling Methods 0.000 description 2
• 230000001275 ca(2+)-mobilization Effects 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
• 239000008116 calcium stearate Substances 0.000 description 2
• 235000013539 calcium stearate Nutrition 0.000 description 2
• 235000014633 carbohydrates Nutrition 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001149 cognitive effect Effects 0.000 description 2
• 230000000052 comparative effect Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 238000000586 desensitisation Methods 0.000 description 2
• 229940111685 dibasic potassium phosphate Drugs 0.000 description 2
• 229940061607 dibasic sodium phosphate Drugs 0.000 description 2
• SNVTZAIYUGUKNI-UHFFFAOYSA-N dibenzo[1,2-a:1',2'-e][7]annulen-11-one Chemical compound C1=CC2=CC=CC=C2C(=O)C2=CC=CC=C21 SNVTZAIYUGUKNI-UHFFFAOYSA-N 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 230000006397 emotional response Effects 0.000 description 2
• 229960004341 escitalopram Drugs 0.000 description 2
• WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• 235000020937 fasting conditions Nutrition 0.000 description 2
• 238000010579 first pass effect Methods 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 229960002870 gabapentin Drugs 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000000174 gluconic acid Substances 0.000 description 2
• 235000012208 gluconic acid Nutrition 0.000 description 2
• 230000023611 glucuronidation Effects 0.000 description 2
• 210000003709 heart valve Anatomy 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 230000010224 hepatic metabolism Effects 0.000 description 2
• 208000002672 hepatitis B Diseases 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 230000000147 hypnotic effect Effects 0.000 description 2
• 150000002454 idoses Chemical class 0.000 description 2
• 238000011081 inoculation Methods 0.000 description 2
• 230000002452 interceptive effect Effects 0.000 description 2
• 210000004731 jugular vein Anatomy 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 238000012417 linear regression Methods 0.000 description 2
• 235000019421 lipase Nutrition 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 229940045641 monobasic sodium phosphate Drugs 0.000 description 2
• 230000036651 mood Effects 0.000 description 2
• 210000004400 mucous membrane Anatomy 0.000 description 2
• 230000000422 nocturnal effect Effects 0.000 description 2
• 230000008452 non REM sleep Effects 0.000 description 2
• 231100000862 numbness Toxicity 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 229940100688 oral solution Drugs 0.000 description 2
• 235000019629 palatability Nutrition 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 230000002085 persistent effect Effects 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 239000008363 phosphate buffer Substances 0.000 description 2
• 229960001233 pregabalin Drugs 0.000 description 2
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 208000020016 psychiatric disease Diseases 0.000 description 2
• 238000012797 qualification Methods 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 238000001525 receptor binding assay Methods 0.000 description 2
• 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 2
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 2
• 230000001568 sexual effect Effects 0.000 description 2
• 102000035025 signaling receptors Human genes 0.000 description 2
• 108091005475 signaling receptors Proteins 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 201000002859 sleep apnea Diseases 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• 229910000162 sodium phosphate Inorganic materials 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 230000009747 swallowing Effects 0.000 description 2
• 230000009897 systematic effect Effects 0.000 description 2
• 239000007916 tablet composition 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
• 150000003512 tertiary amines Chemical group 0.000 description 2
• 230000003867 tiredness Effects 0.000 description 2
• 208000016255 tiredness Diseases 0.000 description 2
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
• NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
• UIKROCXWUNQSPJ-VIFPVBQESA-N (-)-cotinine Chemical compound C1CC(=O)N(C)[C@@H]1C1=CC=CN=C1 UIKROCXWUNQSPJ-VIFPVBQESA-N 0.000 description 1
• GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• OEANUJAFZLQYOD-CXAZCLJRSA-N (2r,3s,4r,5r,6r)-6-[(2r,3r,4r,5r,6r)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](OC)O[C@H](CO)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC)[C@H](C(O)=O)O1 OEANUJAFZLQYOD-CXAZCLJRSA-N 0.000 description 1
• ZFTFOHBYVDOAMH-XNOIKFDKSA-N (2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-3,4-dihydroxy-2-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2-(hydroxymethyl)oxolane-2,3,4-triol Chemical class O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(OC[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 ZFTFOHBYVDOAMH-XNOIKFDKSA-N 0.000 description 1
• XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 1
• WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
• RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
• TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
• OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
• YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
• 108091005435 5-HT6 receptors Proteins 0.000 description 1
• 102100040370 5-hydroxytryptamine receptor 5A Human genes 0.000 description 1
• 101710138069 5-hydroxytryptamine receptor 5A Proteins 0.000 description 1
• 102100040368 5-hydroxytryptamine receptor 6 Human genes 0.000 description 1
• 101710150235 5-hydroxytryptamine receptor 6 Proteins 0.000 description 1
• 230000035502 ADME Effects 0.000 description 1
• 102100037651 AP-2 complex subunit sigma Human genes 0.000 description 1
• 108060003345 Adrenergic Receptor Proteins 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• 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 1
• 244000144730 Amygdalus persica Species 0.000 description 1
• 229920000945 Amylopectin Polymers 0.000 description 1
• 229920000856 Amylose Polymers 0.000 description 1
• 244000099147 Ananas comosus Species 0.000 description 1
• 235000007119 Ananas comosus Nutrition 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 1
• 208000008035 Back Pain Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• 208000003417 Central Sleep Apnea Diseases 0.000 description 1
• 108091006146 Channels Proteins 0.000 description 1
• 229920002101 Chitin Polymers 0.000 description 1
• 229920002567 Chondroitin Polymers 0.000 description 1
• 102000011022 Chorionic Gonadotropin Human genes 0.000 description 1
• 108010062540 Chorionic Gonadotropin Proteins 0.000 description 1
• 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
• 244000223760 Cinnamomum zeylanicum Species 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
• 244000241235 Citrullus lanatus Species 0.000 description 1
• 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
• 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
• 235000005979 Citrus limon Nutrition 0.000 description 1
• 244000131522 Citrus pyriformis Species 0.000 description 1
• 240000000560 Citrus x paradisi Species 0.000 description 1
• 240000007154 Coffea arabica Species 0.000 description 1
• 240000009226 Corylus americana Species 0.000 description 1
• 235000001543 Corylus americana Nutrition 0.000 description 1
• 235000007466 Corylus avellana Nutrition 0.000 description 1
• UIKROCXWUNQSPJ-UHFFFAOYSA-N Cotinine Natural products C1CC(=O)N(C)C1C1=CC=CN=C1 UIKROCXWUNQSPJ-UHFFFAOYSA-N 0.000 description 1
• 235000013175 Crataegus laevigata Nutrition 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
• YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-CBPJZXOFSA-N D-Gulose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-CBPJZXOFSA-N 0.000 description 1
• WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
• LKDRXBCSQODPBY-JDJSBBGDSA-N D-allulose Chemical compound OCC1(O)OC[C@@H](O)[C@@H](O)[C@H]1O LKDRXBCSQODPBY-JDJSBBGDSA-N 0.000 description 1
• YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
• MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
• CIWBSHSKHKDKBQ-DUZGATOHSA-N D-isoascorbic acid Chemical compound OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• ZAQJHHRNXZUBTE-NQXXGFSBSA-N D-ribulose Chemical compound OC[C@@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-NQXXGFSBSA-N 0.000 description 1
• ZAQJHHRNXZUBTE-UHFFFAOYSA-N D-threo-2-Pentulose Natural products OCC(O)C(O)C(=O)CO ZAQJHHRNXZUBTE-UHFFFAOYSA-N 0.000 description 1
• YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 description 1
• ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
• NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
• 229920000045 Dermatan sulfate Polymers 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 206010013496 Disturbance in attention Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010056474 Erythrosis Diseases 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 235000016623 Fragaria vesca Nutrition 0.000 description 1
• 240000009088 Fragaria x ananassa Species 0.000 description 1
• 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
• 229920002670 Fructan Polymers 0.000 description 1
• 229920000855 Fucoidan Polymers 0.000 description 1
• BXEARCKJAZWJTJ-IJCVXDJZSA-N Galactocarolose Natural products OC[C@H](O)[C@@H]1O[C@@H](O[C@H](CO)[C@@H]2O[C@@H](O[C@H](CO)[C@@H]3O[C@@H](O)[C@H](O)[C@@H]3O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H]1O BXEARCKJAZWJTJ-IJCVXDJZSA-N 0.000 description 1
• 240000001238 Gaultheria procumbens Species 0.000 description 1
• 235000007297 Gaultheria procumbens Nutrition 0.000 description 1
• 208000011688 Generalised anxiety disease Diseases 0.000 description 1
• 229920001503 Glucan Polymers 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 101150015707 HTR1A gene Proteins 0.000 description 1
• 101150049624 HTR5A gene Proteins 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 101000806914 Homo sapiens AP-2 complex subunit sigma Proteins 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 229920001908 Hydrogenated starch hydrolysate Polymers 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 208000004044 Hypesthesia 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
• 208000016588 Idiopathic hypersomnia Diseases 0.000 description 1
• 206010061598 Immunodeficiency Diseases 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 229920001202 Inulin Polymers 0.000 description 1
• 206010022998 Irritability Diseases 0.000 description 1
• 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
• 206010023232 Joint swelling Diseases 0.000 description 1
• 108010076876 Keratins Proteins 0.000 description 1
• 102000011782 Keratins Human genes 0.000 description 1
• 208000007976 Ketosis Diseases 0.000 description 1
• 208000003947 Knee Osteoarthritis Diseases 0.000 description 1
• LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
• 208000008930 Low Back Pain Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
• 235000011430 Malus pumila Nutrition 0.000 description 1
• 235000015103 Malus silvestris Nutrition 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229920000057 Mannan Polymers 0.000 description 1
• 235000014749 Mentha crispa Nutrition 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 244000078639 Mentha spicata Species 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 206010027603 Migraine headaches Diseases 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 208000019022 Mood disease Diseases 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 240000005561 Musa balbisiana Species 0.000 description 1
• 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010028836 Neck pain Diseases 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 208000008705 Nocturnal Myoclonus Syndrome Diseases 0.000 description 1
• KYYIDSXMWOZKMP-UHFFFAOYSA-N O-desmethylvenlafaxine Chemical compound C1CCCCC1(O)C(CN(C)C)C1=CC=C(O)C=C1 KYYIDSXMWOZKMP-UHFFFAOYSA-N 0.000 description 1
• BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
• 208000006199 Parasomnias Diseases 0.000 description 1
• AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
• 235000000370 Passiflora edulis Nutrition 0.000 description 1
• 244000288157 Passiflora edulis Species 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229920002230 Pectic acid Polymers 0.000 description 1
• 229920001100 Polydextrose Polymers 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 108010009736 Protein Hydrolysates Proteins 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 235000009827 Prunus armeniaca Nutrition 0.000 description 1
• 244000018633 Prunus armeniaca Species 0.000 description 1
• 235000006040 Prunus persica var persica Nutrition 0.000 description 1
• 208000036992 Psychogenic pain disease Diseases 0.000 description 1
• 239000004373 Pullulan Substances 0.000 description 1
• 229920001218 Pullulan Polymers 0.000 description 1
• 244000294611 Punica granatum Species 0.000 description 1
• 235000014360 Punica granatum Nutrition 0.000 description 1
• 235000014443 Pyrus communis Nutrition 0.000 description 1
• 240000001987 Pyrus communis Species 0.000 description 1
• 208000025535 REM sleep behavior disease Diseases 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000005793 Restless legs syndrome Diseases 0.000 description 1
• 208000025747 Rheumatic disease Diseases 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 206010039203 Road traffic accident Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 240000007651 Rubus glaucus Species 0.000 description 1
• 235000011034 Rubus glaucus Nutrition 0.000 description 1
• 235000009122 Rubus idaeus Nutrition 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 208000022841 Sleep Arousal disease Diseases 0.000 description 1
• 208000005439 Sleep paralysis Diseases 0.000 description 1
• 206010041009 Sleep talking Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 239000004376 Sucralose Substances 0.000 description 1
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
• 235000019486 Sunflower oil Nutrition 0.000 description 1
• SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
• 208000028911 Temporomandibular Joint disease Diseases 0.000 description 1
• 206010043220 Temporomandibular joint syndrome Diseases 0.000 description 1
• 244000299461 Theobroma cacao Species 0.000 description 1
• 235000011941 Tilia x europaea Nutrition 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• 235000009499 Vanilla fragrans Nutrition 0.000 description 1
• 244000263375 Vanilla tahitensis Species 0.000 description 1
• 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
• 235000009754 Vitis X bourquina Nutrition 0.000 description 1
• 235000012333 Vitis X labruscana Nutrition 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 235000014787 Vitis vinifera Nutrition 0.000 description 1
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• MRGQSEDSFXMWBF-UHFFFAOYSA-N [K].[K].[K].[K] Chemical compound [K].[K].[K].[K] MRGQSEDSFXMWBF-UHFFFAOYSA-N 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• 229960000583 acetic acid Drugs 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
• 208000005298 acute pain Diseases 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 150000001323 aldoses Chemical class 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
• VWYANPOOORUCFJ-UHFFFAOYSA-N alpha-Fernenol Chemical compound CC1(C)C(O)CCC2(C)C3=CCC4(C)C5CCC(C(C)C)C5(C)CCC4(C)C3CCC21 VWYANPOOORUCFJ-UHFFFAOYSA-N 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 230000000202 analgesic effect Effects 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 230000001773 anti-convulsant effect Effects 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 229960003965 antiepileptics Drugs 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• YFGHCGITMMYXAQ-LJQANCHMSA-N armodafinil Chemical compound C=1C=CC=CC=1C([S@](=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-LJQANCHMSA-N 0.000 description 1
• 229960004823 armodafinil Drugs 0.000 description 1
• 230000037007 arousal Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 238000007630 basic procedure Methods 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 238000013542 behavioral therapy Methods 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
• 210000000941 bile Anatomy 0.000 description 1
• 238000011953 bioanalysis Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000005178 buccal mucosa Anatomy 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 229960001058 bupropion Drugs 0.000 description 1
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
• 230000003491 cAMP production Effects 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000000828 canola oil Substances 0.000 description 1
• 235000019519 canola oil Nutrition 0.000 description 1
• 235000013736 caramel Nutrition 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
• 229960000623 carbamazepine Drugs 0.000 description 1
• 150000005323 carbonate salts Chemical class 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 239000000679 carrageenan Substances 0.000 description 1
• 229940113118 carrageenan Drugs 0.000 description 1
• 208000014486 central sleep apnea syndrome Diseases 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 235000019219 chocolate Nutrition 0.000 description 1
• DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
• 235000017803 cinnamon Nutrition 0.000 description 1
• 229960001653 citalopram Drugs 0.000 description 1
• 238000003759 clinical diagnosis Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 235000016213 coffee Nutrition 0.000 description 1
• 235000013353 coffee beverage Nutrition 0.000 description 1
• 238000009226 cognitive therapy Methods 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 239000005356 container glass Substances 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 229950006073 cotinine Drugs 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 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 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 201000001098 delayed sleep phase syndrome Diseases 0.000 description 1
• 208000033921 delayed sleep phase type circadian rhythm sleep disease Diseases 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 229960001623 desvenlafaxine Drugs 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 235000019621 digestibility Nutrition 0.000 description 1
• QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
• PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000003113 dilution method Methods 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 239000007919 dispersible tablet Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 230000036267 drug metabolism Effects 0.000 description 1
• 238000007580 dry-mixing Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229960002866 duloxetine Drugs 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 235000013399 edible fruits Nutrition 0.000 description 1
• 230000004970 emotional disturbance Effects 0.000 description 1
• 235000010350 erythorbic acid Nutrition 0.000 description 1
• UQPHVQVXLPRNCX-UHFFFAOYSA-N erythrulose Chemical compound OCC(O)C(=O)CO UQPHVQVXLPRNCX-UHFFFAOYSA-N 0.000 description 1
• MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 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
• 230000007717 exclusion Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000013213 extrapolation Methods 0.000 description 1
• 230000004424 eye movement Effects 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 229940099283 flexeril Drugs 0.000 description 1
• 229960002464 fluoxetine Drugs 0.000 description 1
• 229960004038 fluvoxamine Drugs 0.000 description 1
• CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 208000029364 generalized anxiety disease Diseases 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229950006191 gluconic acid Drugs 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 229930182480 glucuronide Natural products 0.000 description 1
• 150000008134 glucuronides Chemical class 0.000 description 1
• 150000004676 glycans Polymers 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 150000002337 glycosamines Chemical class 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 150000002386 heptoses Chemical class 0.000 description 1
• 150000002402 hexoses Chemical class 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• 101150075901 htr2 gene Proteins 0.000 description 1
• 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 206010020765 hypersomnia Diseases 0.000 description 1
• 239000003326 hypnotic agent Substances 0.000 description 1
• 208000034783 hypoesthesia Diseases 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 239000012728 immediate-release (IR) tablet Substances 0.000 description 1
• 230000007813 immunodeficiency Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 150000004001 inositols Chemical class 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 229940029339 inulin Drugs 0.000 description 1
• JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• 208000033923 irregular sleep wake type circadian rhythm sleep disease Diseases 0.000 description 1
• 229940026239 isoascorbic acid Drugs 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 235000021579 juice concentrates Nutrition 0.000 description 1
• BJHIKXHVCXFQLS-PQLUHFTBSA-N keto-D-tagatose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)C(=O)CO BJHIKXHVCXFQLS-PQLUHFTBSA-N 0.000 description 1
• 150000002584 ketoses Chemical class 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
• 229960001848 lamotrigine Drugs 0.000 description 1
• AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 description 1
• 229940059904 light mineral oil Drugs 0.000 description 1
• 239000004571 lime Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 210000001853 liver microsome Anatomy 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 238000011866 long-term treatment Methods 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 208000024714 major depressive disease Diseases 0.000 description 1
• LUEWUZLMQUOBSB-GFVSVBBRSA-N mannan Chemical class 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]2[C@H](O[C@@H](O[C@H]3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-GFVSVBBRSA-N 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000009245 menopause Effects 0.000 description 1
• 229940041616 menthol Drugs 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
• HOVAGTYPODGVJG-ZFYZTMLRSA-N methyl alpha-D-glucopyranoside Chemical compound CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HOVAGTYPODGVJG-ZFYZTMLRSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 229960000600 milnacipran Drugs 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 229960001165 modafinil Drugs 0.000 description 1
• 210000002200 mouth mucosa Anatomy 0.000 description 1
• 208000015001 muscle soreness Diseases 0.000 description 1
• 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 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
• 201000003631 narcolepsy Diseases 0.000 description 1
• 210000002850 nasal mucosa Anatomy 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000007372 neural signaling Effects 0.000 description 1
• 210000000826 nictitating membrane Anatomy 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 230000002474 noradrenergic effect Effects 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 208000001797 obstructive sleep apnea Diseases 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 229940127240 opiate Drugs 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
• 229960001816 oxcarbazepine Drugs 0.000 description 1
• 239000005022 packaging material Substances 0.000 description 1
• 229960005489 paracetamol Drugs 0.000 description 1
• 229960002296 paroxetine Drugs 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 150000002972 pentoses Chemical class 0.000 description 1
• 208000023515 periodic limb movement disease Diseases 0.000 description 1
• NFBAXHOPROOJAW-UHFFFAOYSA-N phenindione Chemical compound O=C1C2=CC=CC=C2C(=O)C1C1=CC=CC=C1 NFBAXHOPROOJAW-UHFFFAOYSA-N 0.000 description 1
• 229960000280 phenindione Drugs 0.000 description 1
• 239000008055 phosphate buffer solution Substances 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 1
• 235000013856 polydextrose Nutrition 0.000 description 1
• 239000001259 polydextrose Substances 0.000 description 1
• 229940035035 polydextrose Drugs 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 150000004804 polysaccharides Polymers 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229960003975 potassium Drugs 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229960002635 potassium citrate Drugs 0.000 description 1
• 235000011082 potassium citrates Nutrition 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
• 229960003089 pramipexole Drugs 0.000 description 1
• IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical group N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
• 229960001289 prazosin Drugs 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 235000019423 pullulan Nutrition 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 239000013074 reference sample Substances 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000002787 reinforcement Effects 0.000 description 1
• 238000012958 reprocessing Methods 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• 230000001020 rhythmical effect Effects 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000000862 serotonergic effect Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000003860 sleep quality Effects 0.000 description 1
• 230000037321 sleepiness Effects 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 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
• 235000011083 sodium citrates Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 229960003928 sodium oxybate Drugs 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229940080313 sodium starch Drugs 0.000 description 1
• 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 235000019408 sucralose Nutrition 0.000 description 1
• BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000002600 sunflower oil Substances 0.000 description 1
• 235000019605 sweet taste sensations Nutrition 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
• 238000012353 t test Methods 0.000 description 1
• 229960003188 temazepam Drugs 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
• 229960001918 tiagabine Drugs 0.000 description 1
• OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 229960004380 tramadol Drugs 0.000 description 1
• TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 229960003991 trazodone Drugs 0.000 description 1
• PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000004043 trisaccharides Chemical class 0.000 description 1
• 230000007306 turnover Effects 0.000 description 1
• 229940102566 valproate Drugs 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 229960004688 venlafaxine Drugs 0.000 description 1
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 230000036642 wellbeing Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229920001221 xylan Polymers 0.000 description 1
• 150000004823 xylans Chemical class 0.000 description 1
• 235000010447 xylitol Nutrition 0.000 description 1
• 239000000811 xylitol Substances 0.000 description 1
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
• 229960002675 xylitol Drugs 0.000 description 1
• HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 description 1
• 229960004010 zaleplon Drugs 0.000 description 1
• 239000011787 zinc oxide Substances 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 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
• ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
• 229960001475 zolpidem Drugs 0.000 description 1