PT1877390E - Compostos benzisoxazole-piridina e métodos para a sua utilização - Google Patents

Info

Publication number

PT1877390E

PT1877390E PT06751667T PT06751667T PT1877390E PT 1877390 E PT1877390 E PT 1877390E PT 06751667 T PT06751667 T PT 06751667T PT 06751667 T PT06751667 T PT 06751667T PT 1877390 E PT1877390 E PT 1877390E

Authority

PT

Portugal

Prior art keywords

quot

sleep

compound

compounds

treatment

Prior art date

2005-04-26

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title abstract description 18
• GAHWPVPYFSNWOU-UHFFFAOYSA-N 1,2-benzoxazole;piperazine Chemical class C1CNCCN1.C1=CC=C2C=NOC2=C1 GAHWPVPYFSNWOU-UHFFFAOYSA-N 0.000 title description 2
• 239000000203 mixture Substances 0.000 claims abstract description 41
• 150000001875 compounds Chemical class 0.000 claims description 251
• 238000011282 treatment Methods 0.000 claims description 90
• 239000003814 drug Substances 0.000 claims description 55
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 47
• 206010022437 insomnia Diseases 0.000 claims description 46
• 150000003839 salts Chemical class 0.000 claims description 38
• 208000019116 sleep disease Diseases 0.000 claims description 37
• 125000000217 alkyl group Chemical group 0.000 claims description 36
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
• 229940079593 drug Drugs 0.000 claims description 29
• 208000035475 disorder Diseases 0.000 claims description 26
• 229940124597 therapeutic agent Drugs 0.000 claims description 21
• 208000020685 sleep-wake disease Diseases 0.000 claims description 19
• 238000009472 formulation Methods 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
• 238000002560 therapeutic procedure Methods 0.000 claims description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 201000002859 sleep apnea Diseases 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 239000001301 oxygen Chemical group 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• 150000003536 tetrazoles Chemical class 0.000 claims description 8
• 230000027288 circadian rhythm Effects 0.000 claims description 7
• 125000003003 spiro group Chemical group 0.000 claims description 7
• 208000006199 Parasomnias Diseases 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011593 sulfur Chemical group 0.000 claims description 5
• 230000036541 health Effects 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 3
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
• 206010020765 hypersomnia Diseases 0.000 claims description 3
• 201000003631 narcolepsy Diseases 0.000 claims description 3
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 229910052698 phosphorus Chemical group 0.000 claims description 2
• 239000011574 phosphorus Chemical group 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
• 230000007958 sleep Effects 0.000 abstract description 146
• RRNFVWZCXHFAEE-UHFFFAOYSA-N 1,2-benzoxazole;piperidine Chemical compound C1CCNCC1.C1=CC=C2C=NOC2=C1 RRNFVWZCXHFAEE-UHFFFAOYSA-N 0.000 abstract 1
• 238000009739 binding Methods 0.000 description 44
• 230000027455 binding Effects 0.000 description 42
• -1 1,2,3,4-tetrahydronaphthalen-1-yl Chemical group 0.000 description 41
• 230000008452 non REM sleep Effects 0.000 description 41
• 230000000694 effects Effects 0.000 description 34
• 150000008316 benzisoxazoles Chemical class 0.000 description 28
• 238000012360 testing method Methods 0.000 description 25
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 24
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 230000006742 locomotor activity Effects 0.000 description 24
• 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 22
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 21
• 125000003342 alkenyl group Chemical group 0.000 description 21
• 125000003118 aryl group Chemical group 0.000 description 21
• 210000004027 cell Anatomy 0.000 description 21
• 239000000243 solution Substances 0.000 description 20
• 125000000304 alkynyl group Chemical group 0.000 description 19
• 125000000623 heterocyclic group Chemical group 0.000 description 19
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
• 239000003981 vehicle Substances 0.000 description 16
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 15
• 239000012453 solvate Substances 0.000 description 15
• 241001465754 Metazoa Species 0.000 description 14
• 230000036760 body temperature Effects 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 14
• 125000004414 alkyl thio group Chemical group 0.000 description 13
• 230000001186 cumulative effect Effects 0.000 description 13
• 230000001965 increasing effect Effects 0.000 description 13
• 238000000159 protein binding assay Methods 0.000 description 13
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
• 208000002193 Pain Diseases 0.000 description 12
• 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 12
• 150000007942 carboxylates Chemical class 0.000 description 12
• 239000002552 dosage form Substances 0.000 description 12
• 125000004429 atom Chemical group 0.000 description 11
• 125000001072 heteroaryl group Chemical group 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• 230000009870 specific binding Effects 0.000 description 11
• 125000001424 substituent group Chemical group 0.000 description 11
• 206010062519 Poor quality sleep Diseases 0.000 description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 10
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• 230000005764 inhibitory process Effects 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical group [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 10
• 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 9
• 239000004480 active ingredient Substances 0.000 description 9
• 125000003282 alkyl amino group Chemical group 0.000 description 9
• 125000000129 anionic group Chemical group 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 125000004093 cyano group Chemical group *C#N 0.000 description 9
• 235000019253 formic acid Nutrition 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 230000004461 rapid eye movement Effects 0.000 description 9
• 229960002646 scopolamine Drugs 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
• 208000019901 Anxiety disease Diseases 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 125000003545 alkoxy group Chemical group 0.000 description 8
• 125000002877 alkyl aryl group Chemical group 0.000 description 8
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 8
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 8
• 125000005110 aryl thio group Chemical group 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 8
• 238000002648 combination therapy Methods 0.000 description 8
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
• 230000008030 elimination Effects 0.000 description 8
• 238000003379 elimination reaction Methods 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 150000002367 halogens Chemical class 0.000 description 8
• 210000003494 hepatocyte Anatomy 0.000 description 8
• 229940002612 prodrug Drugs 0.000 description 8
• 239000000651 prodrug Substances 0.000 description 8
• 230000002685 pulmonary effect Effects 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 8
• 238000003419 tautomerization reaction Methods 0.000 description 8
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 7
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 7
• 241000700157 Rattus norvegicus Species 0.000 description 7
• 125000004442 acylamino group Chemical group 0.000 description 7
• 239000000443 aerosol Substances 0.000 description 7
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 7
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
• 125000005199 aryl carbonyloxy group Chemical group 0.000 description 7
• 230000002060 circadian Effects 0.000 description 7
• 238000007596 consolidation process Methods 0.000 description 7
• 125000004663 dialkyl amino group Chemical group 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• 150000003467 sulfuric acid derivatives Chemical group 0.000 description 7
• 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 6
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 6
• STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• 125000002252 acyl group Chemical group 0.000 description 6
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 6
• 125000004947 alkyl aryl amino group Chemical group 0.000 description 6
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
• 230000036506 anxiety Effects 0.000 description 6
• 125000001769 aryl amino group Chemical group 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000009286 beneficial effect Effects 0.000 description 6
• 238000004364 calculation method Methods 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 208000015114 central nervous system disease Diseases 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 description 6
• 125000004986 diarylamino group Chemical group 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 230000000147 hypnotic effect Effects 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 230000004048 modification Effects 0.000 description 6
• 238000012986 modification Methods 0.000 description 6
• 239000013641 positive control Substances 0.000 description 6
• STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 6
• 125000004434 sulfur atom Chemical group 0.000 description 6
• 230000002618 waking effect Effects 0.000 description 6
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 5
• 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 230000001078 anti-cholinergic effect Effects 0.000 description 5
• 239000000739 antihistaminic agent Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 230000003542 behavioural effect Effects 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 230000008499 blood brain barrier function Effects 0.000 description 5
• 210000001218 blood-brain barrier Anatomy 0.000 description 5
• 230000008859 change Effects 0.000 description 5
• 125000000524 functional group Chemical group 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 239000003326 hypnotic agent Substances 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 238000007918 intramuscular administration Methods 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• 208000020016 psychiatric disease Diseases 0.000 description 5
• 230000002557 soporific effect Effects 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
• 241000271566 Aves Species 0.000 description 4
• 108091006146 Channels Proteins 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 208000001456 Jet Lag Syndrome Diseases 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 208000005793 Restless legs syndrome Diseases 0.000 description 4
• 208000010340 Sleep Deprivation Diseases 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 229940125715 antihistaminic agent Drugs 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 230000001713 cholinergic effect Effects 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 230000003111 delayed effect Effects 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• 229960003638 dopamine Drugs 0.000 description 4
• GBBSUAFBMRNDJC-INIZCTEOSA-N eszopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-INIZCTEOSA-N 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 230000001976 improved effect Effects 0.000 description 4
• 238000007912 intraperitoneal administration Methods 0.000 description 4
• 238000007913 intrathecal administration Methods 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 4
• 238000012423 maintenance Methods 0.000 description 4
• 238000012544 monitoring process Methods 0.000 description 4
• 230000003551 muscarinic effect Effects 0.000 description 4
• 210000001331 nose Anatomy 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 239000000932 sedative agent Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• WWJHRSCUAQPFQO-UHFFFAOYSA-M 4-DAMP methiodide Chemical compound [I-].C1C[N+](C)(C)CCC1OC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 WWJHRSCUAQPFQO-UHFFFAOYSA-M 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000001640 Fibromyalgia Diseases 0.000 description 3
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101150104779 HTR2A gene Proteins 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 208000004454 Hyperalgesia Diseases 0.000 description 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 208000019022 Mood disease Diseases 0.000 description 3
• 208000012902 Nervous system disease Diseases 0.000 description 3
• 208000025966 Neurological disease Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 238000009825 accumulation Methods 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 125000005129 aryl carbonyl group Chemical group 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
• 230000000747 cardiac effect Effects 0.000 description 3
• 150000001768 cations Chemical class 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000012377 drug delivery Methods 0.000 description 3
• 230000002349 favourable effect Effects 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 239000003365 glass fiber Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000007943 implant Substances 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 244000144972 livestock Species 0.000 description 3
• 229920000609 methyl cellulose Polymers 0.000 description 3
• 229940050176 methyl chloride Drugs 0.000 description 3
• 239000001923 methylcellulose Substances 0.000 description 3
• 229960001383 methylscopolamine Drugs 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 210000000214 mouth Anatomy 0.000 description 3
• 208000004296 neuralgia Diseases 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• 125000004437 phosphorous atom Chemical group 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002035 prolonged effect Effects 0.000 description 3
• 235000018102 proteins Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 239000002287 radioligand Substances 0.000 description 3
• CXYRUNPLKGGUJF-RAFJPFSSSA-M scopolamine methobromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 CXYRUNPLKGGUJF-RAFJPFSSSA-M 0.000 description 3
• 229940125723 sedative agent Drugs 0.000 description 3
• 230000001624 sedative effect Effects 0.000 description 3
• 238000009097 single-agent therapy Methods 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 229910001220 stainless steel Inorganic materials 0.000 description 3
• 239000010935 stainless steel Substances 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 125000000547 substituted alkyl group Chemical group 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000003828 vacuum filtration Methods 0.000 description 3
• GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
• 108060003345 Adrenergic Receptor Proteins 0.000 description 2
• 102000017910 Adrenergic receptor Human genes 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 241000700198 Cavia Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 206010052804 Drug tolerance Diseases 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 208000035154 Hyperesthesia Diseases 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 208000019695 Migraine disease Diseases 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 206010029333 Neurosis Diseases 0.000 description 2
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
• 206010041347 Somnambulism Diseases 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
• 229930006000 Sucrose Natural products 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
• 206010052428 Wound Diseases 0.000 description 2
• 230000005856 abnormality Effects 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 238000011374 additional therapy Methods 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 125000003158 alcohol group Chemical group 0.000 description 2
• 125000002723 alicyclic group Chemical group 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 239000003416 antiarrhythmic agent Substances 0.000 description 2
• 239000001961 anticonvulsive agent Substances 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000003435 aroyl group Chemical group 0.000 description 2
• 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 description 2
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000007177 brain activity Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 238000011088 calibration curve Methods 0.000 description 2
• 239000006285 cell suspension Substances 0.000 description 2
• 238000007635 classification algorithm Methods 0.000 description 2
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000005595 deprotonation Effects 0.000 description 2
• 238000010537 deprotonation reaction Methods 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 230000035622 drinking Effects 0.000 description 2
• 238000009510 drug design Methods 0.000 description 2
• 206010013781 dry mouth Diseases 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 229960001578 eszopiclone Drugs 0.000 description 2
• 210000000744 eyelid Anatomy 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• 230000033001 locomotion Effects 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 238000002483 medication Methods 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 208000021722 neuropathic pain Diseases 0.000 description 2
• 208000015238 neurotic disease Diseases 0.000 description 2
• 230000000422 nocturnal effect Effects 0.000 description 2
• 208000001797 obstructive sleep apnea Diseases 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 2
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 2
• 229960004633 pirenzepine Drugs 0.000 description 2
• 230000036470 plasma concentration Effects 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920001282 polysaccharide Polymers 0.000 description 2
• 239000005017 polysaccharide Substances 0.000 description 2
• 150000004804 polysaccharides Chemical class 0.000 description 2
• 244000144977 poultry Species 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
• 239000003380 propellant Substances 0.000 description 2
• 230000005588 protonation Effects 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000002336 repolarization Effects 0.000 description 2
• 210000002345 respiratory system Anatomy 0.000 description 2
• 230000033764 rhythmic process Effects 0.000 description 2
• RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 208000022925 sleep disturbance Diseases 0.000 description 2
• 230000004617 sleep duration Effects 0.000 description 2
• 230000003860 sleep quality Effects 0.000 description 2
• 230000004622 sleep time Effects 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 150000008054 sulfonate salts Chemical group 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 230000003797 telogen phase Effects 0.000 description 2
• 229960000351 terfenadine Drugs 0.000 description 2
• 150000003568 thioethers Chemical class 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 238000009736 wetting Methods 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• 229960000820 zopiclone Drugs 0.000 description 2
• OIMYVGPSYULCLE-UHFFFAOYSA-N 1,2-benzoxazole pyridine Chemical class N1=CC=CC=C1.O1N=CC2=C1C=CC=C2 OIMYVGPSYULCLE-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• VXRDAMSNTXUHFX-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide Chemical compound OC(=O)C(O)C(O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 VXRDAMSNTXUHFX-UHFFFAOYSA-N 0.000 description 1
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
• VRHJBWUIWQOFLF-WLHGVMLRSA-N 2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 VRHJBWUIWQOFLF-WLHGVMLRSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 1
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• INWUFXPCLZRSBH-UHFFFAOYSA-N 3-chloro-1,2-benzoxazole Chemical compound C1=CC=C2C(Cl)=NOC2=C1 INWUFXPCLZRSBH-UHFFFAOYSA-N 0.000 description 1
• PPGXDBJURPEKDZ-UHFFFAOYSA-N 3-ethoxychromen-2-one Chemical compound C1=CC=C2OC(=O)C(OCC)=CC2=C1 PPGXDBJURPEKDZ-UHFFFAOYSA-N 0.000 description 1
• ZDFQBFVFCPABKQ-UHFFFAOYSA-N 3-piperazin-1-yl-1,2-benzoxazole Chemical compound C1CNCCN1C1=NOC2=CC=CC=C12 ZDFQBFVFCPABKQ-UHFFFAOYSA-N 0.000 description 1
• PEPBFCOIJRULGJ-UHFFFAOYSA-N 3h-1,2,3-benzodioxazole Chemical compound C1=CC=C2NOOC2=C1 PEPBFCOIJRULGJ-UHFFFAOYSA-N 0.000 description 1
• 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
• IYTJRMRETHPZAC-UHFFFAOYSA-N 4,4-dibenzylpiperidine Chemical compound C1CNCCC1(CC=1C=CC=CC=1)CC1=CC=CC=C1 IYTJRMRETHPZAC-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• XWSCOGPKWVNQSV-UHFFFAOYSA-N 5-bromo-2,3-dichloropyridine Chemical compound ClC1=CC(Br)=CN=C1Cl XWSCOGPKWVNQSV-UHFFFAOYSA-N 0.000 description 1
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• PDBXHPORMXSXKO-UHFFFAOYSA-N 8-benzyl-7-[2-[ethyl(2-hydroxyethyl)amino]ethyl]-1,3-dimethylpurine-2,6-dione;hydron;chloride Chemical class Cl.N=1C=2N(C)C(=O)N(C)C(=O)C=2N(CCN(CCO)CC)C=1CC1=CC=CC=C1 PDBXHPORMXSXKO-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000007848 Alcoholism Diseases 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
• 102100034452 Alternative prion protein Human genes 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 235000017060 Arachis glabrata Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000018262 Arachis monticola Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000025978 Athletic injury Diseases 0.000 description 1
• 208000008035 Back Pain Diseases 0.000 description 1
• 208000020925 Bipolar disease Diseases 0.000 description 1
• 208000031872 Body Remains Diseases 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• 102000017927 CHRM1 Human genes 0.000 description 1
• 102000017926 CHRM2 Human genes 0.000 description 1
• 102000017925 CHRM3 Human genes 0.000 description 1
• 101150060249 CHRM3 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 208000001387 Causalgia Diseases 0.000 description 1
• 208000003417 Central Sleep Apnea Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 101150073075 Chrm1 gene Proteins 0.000 description 1
• 101150012960 Chrm2 gene Proteins 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 235000001258 Cinchona calisaya Nutrition 0.000 description 1
• 206010010774 Constipation Diseases 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 206010012218 Delirium Diseases 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 206010012335 Dependence Diseases 0.000 description 1
• 208000020401 Depressive disease Diseases 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 206010049119 Emotional distress Diseases 0.000 description 1
• 108010055325 EphB3 Receptor Proteins 0.000 description 1
• 102100031982 Ephrin type-B receptor 3 Human genes 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• 208000008454 Hyperhidrosis Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010021118 Hypotonia Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 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 1
• CBIAWPMZSFFRGN-UHFFFAOYSA-N Indiplon Chemical compound CC(=O)N(C)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C(=O)C=2SC=CC=2)=C1 CBIAWPMZSFFRGN-UHFFFAOYSA-N 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 208000007914 Labor Pain Diseases 0.000 description 1
• 208000035945 Labour pain Diseases 0.000 description 1
• 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 1
• 208000009612 Laryngismus Diseases 0.000 description 1
• 206010023891 Laryngospasm Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 102000007205 Muscarinic M2 Receptor Human genes 0.000 description 1
• 108010008407 Muscarinic M2 Receptor Proteins 0.000 description 1
• 208000007379 Muscle Hypotonia Diseases 0.000 description 1
• 208000002033 Myoclonus Diseases 0.000 description 1
• YLXDSYKOBKBWJQ-LBPRGKRZSA-N N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e]benzofuran-8-yl]ethyl]propanamide Chemical compound C1=C2OCCC2=C2[C@H](CCNC(=O)CC)CCC2=C1 YLXDSYKOBKBWJQ-LBPRGKRZSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 208000000224 Night Terrors Diseases 0.000 description 1
• 208000008705 Nocturnal Myoclonus Syndrome Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000027089 Parkinsonian disease Diseases 0.000 description 1
• 206010034010 Parkinsonism Diseases 0.000 description 1
• 208000008469 Peptic Ulcer Diseases 0.000 description 1
• 208000004983 Phantom Limb Diseases 0.000 description 1
• 206010056238 Phantom pain Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
• 208000004550 Postoperative Pain Diseases 0.000 description 1
• 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 1
• 102000004257 Potassium Channel Human genes 0.000 description 1
• 108091000054 Prion Proteins 0.000 description 1
• 208000028017 Psychotic disease Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 208000025535 REM sleep behavior disease Diseases 0.000 description 1
• 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
• 206010038678 Respiratory depression Diseases 0.000 description 1
• 201000001880 Sexual dysfunction Diseases 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 208000007302 Sleep Bruxism Diseases 0.000 description 1
• 206010041010 Sleep terror Diseases 0.000 description 1
• 206010041235 Snoring Diseases 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• 206010041738 Sports injury Diseases 0.000 description 1
• 239000000219 Sympatholytic Substances 0.000 description 1
• 229920006362 Teflon® Polymers 0.000 description 1
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
• 244000269722 Thea sinensis Species 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 208000018452 Torsade de pointes Diseases 0.000 description 1
• 208000002363 Torsades de Pointes Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
• 102000002852 Vasopressins Human genes 0.000 description 1
• 108010004977 Vasopressins Proteins 0.000 description 1
• 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 241000269370 Xenopus <genus> Species 0.000 description 1
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
• JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 201000007034 advanced sleep phase syndrome Diseases 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 201000007930 alcohol dependence Diseases 0.000 description 1
• 125000003172 aldehyde group Chemical group 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 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
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000005089 alkenylaminocarbonyl group Chemical group 0.000 description 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 1
• 125000005157 alkyl carboxy group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 206010053552 allodynia Diseases 0.000 description 1
• 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
• 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229940094070 ambien Drugs 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 230000003288 anthiarrhythmic effect Effects 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000001022 anti-muscarinic effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 239000003529 anticholesteremic agent Substances 0.000 description 1
• 229940127226 anticholesterol agent Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 229940125714 antidiarrheal agent Drugs 0.000 description 1
• 239000003793 antidiarrheal agent Substances 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000003409 antileprotic agent Substances 0.000 description 1
• 239000003430 antimalarial agent Substances 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 239000000164 antipsychotic agent Substances 0.000 description 1
• 239000002221 antipyretic Substances 0.000 description 1
• 229940125716 antipyretic agent Drugs 0.000 description 1
• 239000002216 antistatic agent Substances 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
• 229940125717 barbiturate Drugs 0.000 description 1
• UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 229960004853 betadex Drugs 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000001851 biosynthetic effect Effects 0.000 description 1
• 208000028683 bipolar I disease Diseases 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 239000012888 bovine serum Substances 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 210000003123 bronchiole Anatomy 0.000 description 1
• 229940124630 bronchodilator Drugs 0.000 description 1
• 239000000168 bronchodilator agent Substances 0.000 description 1
• 239000007975 buffered saline Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 238000004422 calculation algorithm Methods 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 239000007958 cherry flavor Substances 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229960004170 clozapine Drugs 0.000 description 1
• 229940068796 clozaril Drugs 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000009226 cognitive therapy Methods 0.000 description 1
• UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 230000001447 compensatory effect Effects 0.000 description 1
• 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
• 208000020020 complex sleep apnea Diseases 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 229940124558 contraceptive agent Drugs 0.000 description 1
• 239000003433 contraceptive agent Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000013256 coordination polymer Substances 0.000 description 1
• 239000003218 coronary vasodilator agent Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 238000011262 co‐therapy Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005070 decynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000003412 degenerative effect 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
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 150000004683 dihydrates Chemical class 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 208000024732 dysthymic disease Diseases 0.000 description 1
• 208000010118 dystonia Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000000517 effect on sleep Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 230000001667 episodic effect Effects 0.000 description 1
• VAIOZOCLKVMIMN-PRJWTAEASA-N eplivanserin Chemical compound C=1C=CC=C(F)C=1\C(=N/OCCN(C)C)\C=C\C1=CC=C(O)C=C1 VAIOZOCLKVMIMN-PRJWTAEASA-N 0.000 description 1
• 229950000789 eplivanserin Drugs 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 201000006061 fatal familial insomnia Diseases 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 239000000417 fungicide Substances 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000002070 germicidal effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000010030 glucose lowering effect Effects 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000026781 habituation Effects 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• VNDHXHMRJVTMTK-WZVRVNPQSA-H hexasodium 4-[[(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecahydroxy-10-(hydroxymethyl)-15,20,25,30,35-pentakis(4-sulfonatobutoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methoxy]butane-1-sulfonate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].OC[C@H]1O[C@@H]2O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]1[C@H](O)[C@H]2O VNDHXHMRJVTMTK-WZVRVNPQSA-H 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
• 230000037315 hyperhidrosis Effects 0.000 description 1
• 210000003026 hypopharynx Anatomy 0.000 description 1
• 150000002466 imines Chemical group 0.000 description 1
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 229950003867 indiplon Drugs 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000016507 interphase Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960001375 lactose Drugs 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229940012618 lunesta Drugs 0.000 description 1
• 229940009697 lyrica Drugs 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960003987 melatonin Drugs 0.000 description 1
• DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000028161 membrane depolarization Effects 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 230000005906 menstruation Effects 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
• 230000004060 metabolic process Effects 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• XFKYUMYFILZJGG-UHFFFAOYSA-N methyl 2,2-dimethyl-3-oxopropanoate Chemical compound COC(=O)C(C)(C)C=O XFKYUMYFILZJGG-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 201000006646 mixed sleep apnea Diseases 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 201000003152 motion sickness Diseases 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 230000000978 myorelaxation Effects 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• 229940072228 neurontin Drugs 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 208000005346 nocturnal enuresis Diseases 0.000 description 1
• 238000013546 non-drug therapy Methods 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005071 nonynyl group Chemical group C(#CCCCCCCC)* 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 229960005017 olanzapine Drugs 0.000 description 1
• 230000000771 oncological effect Effects 0.000 description 1
• 230000000174 oncolytic effect Effects 0.000 description 1
• 210000000287 oocyte Anatomy 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 210000003300 oropharynx Anatomy 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 208000019906 panic disease Diseases 0.000 description 1
• 230000000803 paradoxical effect Effects 0.000 description 1
• 210000003695 paranasal sinus Anatomy 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 238000003909 pattern recognition Methods 0.000 description 1
• 235000020232 peanut Nutrition 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 208000011906 peptic ulcer disease Diseases 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• 208000023515 periodic limb movement disease Diseases 0.000 description 1
• 210000003200 peritoneal cavity Anatomy 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• 238000001126 phototherapy Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 150000004885 piperazines Chemical class 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 229920000570 polyether Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 150000003109 potassium Chemical class 0.000 description 1
• 229940068988 potassium aspartate Drugs 0.000 description 1
• 108020001213 potassium channel Proteins 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 238000000634 powder X-ray diffraction Methods 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 229960001233 pregabalin Drugs 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 229940126532 prescription medicine Drugs 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 238000002203 pretreatment Methods 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 150000004040 pyrrolidinones Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 229960005197 quetiapine fumarate Drugs 0.000 description 1
• 229960000948 quinine Drugs 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 229960001150 ramelteon Drugs 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 239000002469 receptor inverse agonist Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000000246 remedial effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 229940106887 risperdal Drugs 0.000 description 1
• 229960001534 risperidone Drugs 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
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 230000009291 secondary effect Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 229940035004 seroquel Drugs 0.000 description 1
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical class C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 1
• 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 231100000872 sexual dysfunction Toxicity 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 230000004620 sleep latency Effects 0.000 description 1
• 230000008667 sleep stage Effects 0.000 description 1
• 238000010583 slow cooling Methods 0.000 description 1
• 230000037322 slow-wave sleep Effects 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 229940061368 sonata Drugs 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 230000002048 spasmolytic effect Effects 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 208000005809 status epilepticus Diseases 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 125000005415 substituted alkoxy group Chemical group 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 150000008053 sultones Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
• 230000000948 sympatholitic effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 229930192474 thiophene Chemical group 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 210000003437 trachea Anatomy 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• 238000012384 transportation and delivery Methods 0.000 description 1
• 229960002301 trazodone hydrochloride Drugs 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000003852 triazoles Chemical group 0.000 description 1
• 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 229960003726 vasopressin Drugs 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 208000009935 visceral pain Diseases 0.000 description 1
• 238000011179 visual inspection Methods 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 230000036642 wellbeing Effects 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
• 235000010447 xylitol Nutrition 0.000 description 1
• 229960002675 xylitol Drugs 0.000 description 1
• 229960004010 zaleplon 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
• 229960005111 zolpidem tartrate Drugs 0.000 description 1
• VXRDAMSNTXUHFX-CEAXSRTFSA-N zolpidem tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 VXRDAMSNTXUHFX-CEAXSRTFSA-N 0.000 description 1
• 229940039925 zyprexa Drugs 0.000 description 1