NZ535610A - Use of ranolazine for the preparation of a medicament for the treatment of arrhythmias - Google Patents

Info

Publication number

NZ535610A

NZ535610A NZ535610A NZ53561003A NZ535610A NZ 535610 A NZ535610 A NZ 535610A NZ 535610 A NZ535610 A NZ 535610A NZ 53561003 A NZ53561003 A NZ 53561003A NZ 535610 A NZ535610 A NZ 535610A

Authority

NZ

New Zealand

Prior art keywords

compound

ranolazine

isomer

lower alkyl

pharmaceutically acceptable

Prior art date

2002-04-04

Links

• Espacenet
• Global Dossier
• Discuss

• 206010003119 arrhythmia Diseases 0.000 title claims abstract description 75
• 230000006793 arrhythmia Effects 0.000 title claims abstract description 71
• XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 title claims description 313
• 229960000213 ranolazine Drugs 0.000 title claims description 309
• 239000003814 drug Substances 0.000 title claims description 101
• 238000002360 preparation method Methods 0.000 title description 38
• 238000011282 treatment Methods 0.000 title description 17
• 206010047302 ventricular tachycardia Diseases 0.000 claims abstract description 68
• 208000018452 Torsade de pointes Diseases 0.000 claims abstract description 49
• 208000002363 Torsades de Pointes Diseases 0.000 claims abstract description 49
• 150000001875 compounds Chemical class 0.000 claims description 141
• 239000000203 mixture Substances 0.000 claims description 78
• 229940079593 drug Drugs 0.000 claims description 74
• 150000003839 salts Chemical class 0.000 claims description 63
• 241000124008 Mammalia Species 0.000 claims description 61
• 238000009472 formulation Methods 0.000 claims description 44
• 101000694017 Homo sapiens Sodium channel protein type 5 subunit alpha Proteins 0.000 claims description 25
• 102100027198 Sodium channel protein type 5 subunit alpha Human genes 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 24
• -1 aminocarbonylmethyl Chemical group 0.000 claims description 24
• 230000000747 cardiac effect Effects 0.000 claims description 24
• 102000004310 Ion Channels Human genes 0.000 claims description 21
• 108090000862 Ion Channels Proteins 0.000 claims description 21
• 108090000312 Calcium Channels Proteins 0.000 claims description 20
• 102000003922 Calcium Channels Human genes 0.000 claims description 20
• 239000012730 sustained-release form Substances 0.000 claims description 20
• 238000013268 sustained release Methods 0.000 claims description 19
• 238000004519 manufacturing process Methods 0.000 claims description 18
• 108010052164 Sodium Channels Proteins 0.000 claims description 17
• 230000036470 plasma concentration Effects 0.000 claims description 17
• 102000018674 Sodium Channels Human genes 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 150000002148 esters Chemical class 0.000 claims description 15
• 230000035772 mutation Effects 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
• 125000004414 alkyl thio group Chemical group 0.000 claims description 11
• 239000012458 free base Substances 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 150000002431 hydrogen Chemical group 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 239000002585 base Substances 0.000 claims description 7
• 206010002383 Angina Pectoris Diseases 0.000 claims description 6
• 125000002252 acyl group Chemical group 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 206010010356 Congenital anomaly Diseases 0.000 claims description 5
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• RJNSNFZXAZXOFX-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide;hydron;dichloride Chemical compound Cl.Cl.COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 RJNSNFZXAZXOFX-UHFFFAOYSA-N 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 208000031225 myocardial ischemia Diseases 0.000 claims description 4
• 229910052717 sulfur Chemical group 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 3
• 206010002388 Angina unstable Diseases 0.000 claims description 3
• 201000001068 Prinzmetal angina Diseases 0.000 claims description 3
• 208000007814 Unstable Angina Diseases 0.000 claims description 3
• 230000001010 compromised effect Effects 0.000 claims description 3
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 3
• 208000010125 myocardial infarction Diseases 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 8
• 230000000694 effects Effects 0.000 abstract description 129
• 238000000034 method Methods 0.000 abstract description 57
• 208000001871 Tachycardia Diseases 0.000 abstract description 4
• 230000006794 tachycardia Effects 0.000 abstract description 4
• 208000031352 familial ventricular tachycardia Diseases 0.000 abstract description 3
• 208000012404 paroxysmal familial ventricular fibrillation Diseases 0.000 abstract 1
• 230000036982 action potential Effects 0.000 description 94
• 239000000243 solution Substances 0.000 description 89
• 210000004027 cell Anatomy 0.000 description 81
• 210000002216 heart Anatomy 0.000 description 51
• 230000002336 repolarization Effects 0.000 description 46
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 44
• LOUPRKONTZGTKE-LHHVKLHASA-N quinidine 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-LHHVKLHASA-N 0.000 description 44
• 230000001419 dependent effect Effects 0.000 description 38
• 229960002370 sotalol Drugs 0.000 description 34
• 230000002861 ventricular Effects 0.000 description 32
• 239000004480 active ingredient Substances 0.000 description 28
• 239000011230 binding agent Substances 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• 208000004731 long QT syndrome Diseases 0.000 description 25
• 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 23
• 229960001404 quinidine Drugs 0.000 description 22
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
• ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 21
• 230000001960 triggered effect Effects 0.000 description 21
• 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 20
• 241000282465 Canis Species 0.000 description 20
• 239000011575 calcium Substances 0.000 description 20
• 238000012360 testing method Methods 0.000 description 20
• 150000001412 amines Chemical class 0.000 description 19
• 230000001965 increasing effect Effects 0.000 description 19
• 239000004615 ingredient Substances 0.000 description 19
• 230000002829 reductive effect Effects 0.000 description 19
• 210000001567 regular cardiac muscle cell of ventricle Anatomy 0.000 description 19
• 239000003826 tablet Substances 0.000 description 19
• CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 19
• 229950010357 tetrodotoxin Drugs 0.000 description 19
• CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 19
• 210000000107 myocyte Anatomy 0.000 description 18
• 108091006146 Channels Proteins 0.000 description 17
• 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 17
• 239000007995 HEPES buffer Substances 0.000 description 17
• 239000006185 dispersion Substances 0.000 description 17
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 16
• 229960001031 glucose Drugs 0.000 description 16
• 230000036390 resting membrane potential Effects 0.000 description 16
• 241000282472 Canis lupus familiaris Species 0.000 description 15
• 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 15
• 241000700199 Cavia porcellus Species 0.000 description 14
• 206010015856 Extrasystoles Diseases 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• 238000002474 experimental method Methods 0.000 description 14
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
• 230000002159 abnormal effect Effects 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• 201000006903 long QT syndrome 3 Diseases 0.000 description 13
• 230000033764 rhythmic process Effects 0.000 description 13
• 230000000638 stimulation Effects 0.000 description 13
• 102100037444 Potassium voltage-gated channel subfamily KQT member 1 Human genes 0.000 description 12
• 239000008103 glucose Substances 0.000 description 12
• 238000001802 infusion Methods 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 230000002035 prolonged effect Effects 0.000 description 12
• 210000003742 purkinje fiber Anatomy 0.000 description 12
• 230000009471 action Effects 0.000 description 11
• 238000004090 dissolution Methods 0.000 description 11
• 239000000546 pharmaceutical excipient Substances 0.000 description 11
• SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 11
• 229960001802 phenylephrine Drugs 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 10
• 229910052791 calcium Inorganic materials 0.000 description 10
• 230000003111 delayed effect Effects 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• 208000003734 Supraventricular Tachycardia Diseases 0.000 description 9
• 210000003050 axon Anatomy 0.000 description 9
• 239000002552 dosage form Substances 0.000 description 9
• 231100000673 dose–response relationship Toxicity 0.000 description 9
• 230000005764 inhibitory process Effects 0.000 description 9
• 238000005259 measurement Methods 0.000 description 9
• 230000028161 membrane depolarization Effects 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 230000001225 therapeutic effect Effects 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 8
• 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 8
• 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 8
• 229920002472 Starch Polymers 0.000 description 8
• HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 210000005240 left ventricle Anatomy 0.000 description 8
• 229910001629 magnesium chloride Inorganic materials 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• 235000019698 starch Nutrition 0.000 description 8
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 7
• 101001026226 Homo sapiens Potassium voltage-gated channel subfamily KQT member 1 Proteins 0.000 description 7
• 229940009098 aspartate Drugs 0.000 description 7
• 230000036772 blood pressure Effects 0.000 description 7
• 239000001110 calcium chloride Substances 0.000 description 7
• 235000011148 calcium chloride Nutrition 0.000 description 7
• 229910001628 calcium chloride Inorganic materials 0.000 description 7
• 230000008859 change Effects 0.000 description 7
• 229920001577 copolymer Polymers 0.000 description 7
• 235000019359 magnesium stearate Nutrition 0.000 description 7
• 239000008107 starch Substances 0.000 description 7
• 208000003663 ventricular fibrillation Diseases 0.000 description 7
• 101000583076 Anemonia sulcata Delta-actitoxin-Avd1c Proteins 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 238000010494 dissociation reaction Methods 0.000 description 6
• 230000005593 dissociations Effects 0.000 description 6
• 239000011521 glass Substances 0.000 description 6
• 238000002483 medication Methods 0.000 description 6
• 229920003145 methacrylic acid copolymer Polymers 0.000 description 6
• HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 6
• 229960001597 nifedipine Drugs 0.000 description 6
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
• 229910052700 potassium Inorganic materials 0.000 description 6
• 239000011591 potassium Substances 0.000 description 6
• 230000002441 reversible effect Effects 0.000 description 6
• 238000004904 shortening Methods 0.000 description 6
• 229910001415 sodium ion Inorganic materials 0.000 description 6
• 210000002784 stomach Anatomy 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 239000008215 water for injection Substances 0.000 description 6
• 101001023065 Anemonia viridis Delta-actitoxin-Avd1e 2 Proteins 0.000 description 5
• 101001023066 Anemonia viridis Delta-actitoxin-Avd1e 3 Proteins 0.000 description 5
• 108010011185 KCNQ1 Potassium Channel Proteins 0.000 description 5
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
• 102000004257 Potassium Channel Human genes 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 5
• 238000000540 analysis of variance Methods 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
• 239000008108 microcrystalline cellulose Substances 0.000 description 5
• 229940016286 microcrystalline cellulose Drugs 0.000 description 5
• 229960001412 pentobarbital Drugs 0.000 description 5
• 239000008194 pharmaceutical composition Substances 0.000 description 5
• 239000002831 pharmacologic agent Substances 0.000 description 5
• 108020001213 potassium channel Proteins 0.000 description 5
• 230000035945 sensitivity Effects 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 230000002459 sustained effect Effects 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• 229920001817 Agar Polymers 0.000 description 4
• 206010064571 Gene mutation Diseases 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
• QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 4
• 239000008272 agar Substances 0.000 description 4
• IYIKLHRQXLHMJQ-UHFFFAOYSA-N amiodarone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCCN(CC)CC)C(I)=C1 IYIKLHRQXLHMJQ-UHFFFAOYSA-N 0.000 description 4
• 229960005260 amiodarone Drugs 0.000 description 4
• 239000003416 antiarrhythmic agent Substances 0.000 description 4
• 210000001992 atrioventricular node Anatomy 0.000 description 4
• 230000036471 bradycardia Effects 0.000 description 4
• 239000008364 bulk solution Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 239000002131 composite material Substances 0.000 description 4
• 210000004351 coronary vessel Anatomy 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 230000002999 depolarising effect Effects 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 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 4
• 239000000796 flavoring agent Substances 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 210000002064 heart cell Anatomy 0.000 description 4
• 208000019622 heart disease Diseases 0.000 description 4
• 229920000669 heparin Polymers 0.000 description 4
• 230000002779 inactivation Effects 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 150000002500 ions Chemical class 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 238000012423 maintenance Methods 0.000 description 4
• 229920000609 methyl cellulose Polymers 0.000 description 4
• 239000001923 methylcellulose Substances 0.000 description 4
• 235000010981 methylcellulose Nutrition 0.000 description 4
• 230000036961 partial effect Effects 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 238000000306 qrs interval Methods 0.000 description 4
• 239000010453 quartz Substances 0.000 description 4
• 235000012239 silicon dioxide Nutrition 0.000 description 4
• 230000002269 spontaneous effect Effects 0.000 description 4
• 238000007619 statistical method Methods 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• 230000036962 time dependent Effects 0.000 description 4
• 230000001052 transient effect Effects 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 241000242759 Actiniaria Species 0.000 description 3
• 208000020446 Cardiac disease Diseases 0.000 description 3
• 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 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101000974726 Homo sapiens Potassium voltage-gated channel subfamily E member 1 Proteins 0.000 description 3
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
• 208000019025 Hypokalemia Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 241000772415 Neovison vison Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 102100022755 Potassium voltage-gated channel subfamily E member 1 Human genes 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 229910021607 Silver chloride Inorganic materials 0.000 description 3
• 238000000692 Student's t-test Methods 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• 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 3
• 206010047281 Ventricular arrhythmia Diseases 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 230000002238 attenuated effect Effects 0.000 description 3
• 238000010009 beating Methods 0.000 description 3
• 208000006218 bradycardia Diseases 0.000 description 3
• 229910001424 calcium ion Inorganic materials 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 210000000170 cell membrane Anatomy 0.000 description 3
• 235000010980 cellulose Nutrition 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 230000002255 enzymatic effect Effects 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 238000007667 floating Methods 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 229940117841 methacrylic acid copolymer Drugs 0.000 description 3
• 229940098779 methanesulfonic acid Drugs 0.000 description 3
• 210000004165 myocardium Anatomy 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 238000006386 neutralization reaction Methods 0.000 description 3
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
• 229940124531 pharmaceutical excipient Drugs 0.000 description 3
• 208000024896 potassium deficiency disease Diseases 0.000 description 3
• 238000000718 qrs complex Methods 0.000 description 3
• HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 3
• 229910000162 sodium phosphate Inorganic materials 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 125000005017 substituted alkenyl group Chemical group 0.000 description 3
• 125000000547 substituted alkyl group Chemical group 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 239000003053 toxin Substances 0.000 description 3
• 231100000765 toxin Toxicity 0.000 description 3
• 108700012359 toxins Proteins 0.000 description 3
• 238000005303 weighing Methods 0.000 description 3
• XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 2
• VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 2
• SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 2
• TVZCRIROJQEVOT-LSDHHAIUSA-N (3r,4s)-3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromene-6-carbonitrile Chemical compound N1([C@H]2C3=CC(=CC=C3OC([C@@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-LSDHHAIUSA-N 0.000 description 2
• VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 2
• 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 2
• 206010003658 Atrial Fibrillation Diseases 0.000 description 2
• 206010003662 Atrial flutter Diseases 0.000 description 2
• 206010003671 Atrioventricular Block Diseases 0.000 description 2
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 description 2
• 241000700198 Cavia Species 0.000 description 2
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
• 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 2
• 206010014418 Electrolyte imbalance Diseases 0.000 description 2
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
• 229920003135 Eudragit® L 100-55 Polymers 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-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
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• 206010021027 Hypomagnesaemia Diseases 0.000 description 2
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 101100136062 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) PE10 gene Proteins 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 208000008376 Pre-Excitation Syndromes Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-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
• 206010042434 Sudden death Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
• 208000003443 Unconsciousness Diseases 0.000 description 2
• 201000008803 Wolff-Parkinson-white syndrome Diseases 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• 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 2
• 150000007513 acids Chemical class 0.000 description 2
• 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 229920013820 alkyl cellulose Polymers 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000000844 anti-bacterial effect Effects 0.000 description 2
• 229940121375 antifungal agent Drugs 0.000 description 2
• 239000003429 antifungal agent Substances 0.000 description 2
• GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 210000004413 cardiac myocyte Anatomy 0.000 description 2
• 239000008148 cardioplegic solution Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 229920002301 cellulose acetate Polymers 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 2
• 229960005132 cisapride Drugs 0.000 description 2
• DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 239000007891 compressed tablet Substances 0.000 description 2
• 238000012790 confirmation Methods 0.000 description 2
• 230000008602 contraction Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 235000005687 corn oil Nutrition 0.000 description 2
• 239000002285 corn oil Substances 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 229960000673 dextrose monohydrate Drugs 0.000 description 2
• 230000003205 diastolic effect Effects 0.000 description 2
• 238000009792 diffusion process Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002612 dispersion medium Substances 0.000 description 2
• 239000012153 distilled water Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 230000037024 effective refractory period Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• 230000000763 evoking effect Effects 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 2
• 229960004884 fluconazole Drugs 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 239000013022 formulation composition Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 229940014259 gelatin Drugs 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 208000028867 ischemia Diseases 0.000 description 2
• 229960004130 itraconazole Drugs 0.000 description 2
• 229960004125 ketoconazole Drugs 0.000 description 2
• 229960004194 lidocaine Drugs 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 238000011068 loading method Methods 0.000 description 2
• 210000005244 lower chamber Anatomy 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 229960003404 mexiletine Drugs 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 229960002275 pentobarbital sodium Drugs 0.000 description 2
• 230000010412 perfusion Effects 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
• 150000003021 phthalic acid derivatives Chemical class 0.000 description 2
• 229920000193 polymethacrylate Polymers 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
• 239000004299 sodium benzoate Substances 0.000 description 2
• 235000010234 sodium benzoate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 238000011146 sterile filtration Methods 0.000 description 2
• 239000008223 sterile water Substances 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
• 229960000351 terfenadine Drugs 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 239000000230 xanthan gum Substances 0.000 description 2
• 235000010493 xanthan gum Nutrition 0.000 description 2
• 229920001285 xanthan gum Polymers 0.000 description 2
• 229940082509 xanthan gum Drugs 0.000 description 2
• SKBXVAOMEVOTGJ-UHFFFAOYSA-N xi-Pinol Chemical compound CC1=CCC2C(C)(C)OC1C2 SKBXVAOMEVOTGJ-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-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
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• XFSBVAOIAHNAPC-XTHSEXKGSA-N 16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-XTHSEXKGSA-N 0.000 description 1
• JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-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
• AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
• JCLFHZLOKITRCE-UHFFFAOYSA-N 4-pentoxyphenol Chemical compound CCCCCOC1=CC=C(O)C=C1 JCLFHZLOKITRCE-UHFFFAOYSA-N 0.000 description 1
• RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 1
• XFSBVAOIAHNAPC-UHFFFAOYSA-N Aconitin Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(OC(C)=O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 241000837181 Andina Species 0.000 description 1
• 102100036818 Ankyrin-2 Human genes 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
• 208000006808 Atrioventricular Nodal Reentry Tachycardia Diseases 0.000 description 1
• ISNYUQWBWALXEY-UHFFFAOYSA-N Batrachotoxin Natural products C=1CC2(C3=CCC4C5(C)CCC(C4)(O)OC53C(O)C3)OCCN(C)CC32C=1C(C)OC(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-UHFFFAOYSA-N 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 229920000623 Cellulose acetate phthalate Polymers 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
• 235000001258 Cinchona calisaya Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 240000000560 Citrus x paradisi Species 0.000 description 1
• WPSYTTKBGAZSCX-UHFFFAOYSA-N Clofilium Chemical compound CCCCCCC[N+](CC)(CC)CCCCC1=CC=C(Cl)C=C1 WPSYTTKBGAZSCX-UHFFFAOYSA-N 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 208000002330 Congenital Heart Defects Diseases 0.000 description 1
• 208000027205 Congenital disease Diseases 0.000 description 1
• 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 description 1
• 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 1
• 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 1
• 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 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 229920003153 Eudragit® NE polymer Polymers 0.000 description 1
• 229920003134 Eudragit® polymer Polymers 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101000928344 Homo sapiens Ankyrin-2 Proteins 0.000 description 1
• 101000974720 Homo sapiens Potassium voltage-gated channel subfamily E member 2 Proteins 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• 208000013038 Hypocalcemia Diseases 0.000 description 1
• ALOBUEHUHMBRLE-UHFFFAOYSA-N Ibutilide Chemical compound CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ALOBUEHUHMBRLE-UHFFFAOYSA-N 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-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
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 102000010954 Link domains Human genes 0.000 description 1
• 108050001157 Link domains Proteins 0.000 description 1
• 208000019693 Lung disease 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
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• 235000009421 Myristica fragrans Nutrition 0.000 description 1
• KEECCEWTUVWFCV-UHFFFAOYSA-N N-acetylprocainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(NC(C)=O)C=C1 KEECCEWTUVWFCV-UHFFFAOYSA-N 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 1
• 206010033557 Palpitations Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 102100022752 Potassium voltage-gated channel subfamily E member 2 Human genes 0.000 description 1
• IFFPICMESYHZPQ-UHFFFAOYSA-N Prenylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CCNC(C)CC1=CC=CC=C1 IFFPICMESYHZPQ-UHFFFAOYSA-N 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
• 241000220317 Rosa Species 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 102000005393 Sodium-Potassium-Exchanging ATPase Human genes 0.000 description 1
• 108010006431 Sodium-Potassium-Exchanging ATPase Proteins 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 244000166550 Strophanthus gratus Species 0.000 description 1
• 238000010161 Student-Newman-Keuls test Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 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
• 206010065341 Ventricular tachyarrhythmia Diseases 0.000 description 1
• FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 1
• VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical group [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 229940039750 aconitine Drugs 0.000 description 1
• STDXGNLCJACLFY-UHFFFAOYSA-N aconitine Natural products CCN1CC2(COC)C(O)CC(O)C34C5CC6(O)C(OC)C(O)C(OC(=O)C)(C5C6OC(=O)c7ccccc7)C(C(OC)C23)C14 STDXGNLCJACLFY-UHFFFAOYSA-N 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000001800 adrenalinergic effect Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000005250 alkyl acrylate group Chemical group 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• DCHLNFQWPLNLQG-OWIWTKNASA-N anthopleurin a Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CN)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CN=CN1 DCHLNFQWPLNLQG-OWIWTKNASA-N 0.000 description 1
• 108010058857 anthopleurin-A Proteins 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000007900 aqueous suspension 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
• 229960003121 arginine Drugs 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
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 229960004754 astemizole Drugs 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 206010003668 atrial tachycardia Diseases 0.000 description 1
• 230000003416 augmentation Effects 0.000 description 1
• 230000002567 autonomic effect Effects 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 229910052793 cadmium Inorganic materials 0.000 description 1
• BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 230000001964 calcium overload Effects 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 229960003340 calcium silicate Drugs 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000002327 cardiovascular agent Substances 0.000 description 1
• 229940125692 cardiovascular agent Drugs 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
• 229920003086 cellulose ether Polymers 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 229960002887 deanol Drugs 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 1
• 125000005266 diarylamine group Chemical group 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• FCFZKAVCDNTYID-UHFFFAOYSA-M dibenziodolium chloride Chemical compound [Cl-].C1=CC=C2[I+]C3=CC=CC=C3C2=C1 FCFZKAVCDNTYID-UHFFFAOYSA-M 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
• 239000002866 dihydropyridine calcium channel blocker Substances 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 1
• 229960002994 dofetilide Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 230000000668 effect on calcium Effects 0.000 description 1
• 230000008451 emotion Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 210000003315 endocardial cell Anatomy 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• 229960003276 erythromycin Drugs 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 229960004979 fampridine Drugs 0.000 description 1
• 229960003580 felodipine Drugs 0.000 description 1
• 210000001105 femoral artery Anatomy 0.000 description 1
• 210000003191 femoral vein Anatomy 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 229960002464 fluoxetine 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
• 229960004038 fluvoxamine Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 235000015201 grapefruit juice Nutrition 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000005831 heart abnormality Effects 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 208000027700 hepatic dysfunction Diseases 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229960002885 histidine Drugs 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 230000002102 hyperpolarization Effects 0.000 description 1
• 230000000705 hypocalcaemia Effects 0.000 description 1
• 229960004053 ibutilide Drugs 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
• 229960004569 indapamide Drugs 0.000 description 1
• CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 1
• 229960001936 indinavir Drugs 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 239000011872 intimate mixture Substances 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 230000001788 irregular Effects 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
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000013433 lightheadedness Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 229960001078 lithium Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 239000001115 mace Substances 0.000 description 1
• 239000003120 macrolide antibiotic agent Substances 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005399 mechanical ventilation Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
• ZFLWDHHVRRZMEI-UHFFFAOYSA-N methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1C(F)(F)F ZFLWDHHVRRZMEI-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
• 229960000282 metronidazole Drugs 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• ZBMZVLHSJCTVON-GFCCVEGCSA-N n-[4-[(1s)-1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl]methanesulfonamide Chemical compound CC(C)NC[C@@H](O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-GFCCVEGCSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
• 229960001800 nefazodone Drugs 0.000 description 1
• 229960001783 nicardipine Drugs 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000000820 nonprescription drug Substances 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 229940053544 other antidepressants in atc Drugs 0.000 description 1
• LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
• 229960003343 ouabain Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000004963 pathophysiological condition Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• 229960002310 pinacidil Drugs 0.000 description 1
• 239000002985 plastic film Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
• 239000003450 potassium channel blocker Substances 0.000 description 1
• 229910001414 potassium ion Inorganic materials 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 229960001989 prenylamine Drugs 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000001536 pro-arrhythmogenic effect Effects 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
• 230000000644 propagated effect Effects 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 229940076788 pyruvate Drugs 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 229960000948 quinine Drugs 0.000 description 1
• 238000007674 radiofrequency ablation Methods 0.000 description 1
• 230000036279 refractory period Effects 0.000 description 1
• 230000004213 regulation of atrial cardiomyocyte membrane depolarization Effects 0.000 description 1
• 230000034225 regulation of ventricular cardiomyocyte membrane depolarization Effects 0.000 description 1
• 230000013577 regulation of ventricular cardiomyocyte membrane repolarization Effects 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000001020 rhythmical effect Effects 0.000 description 1
• 210000005241 right ventricle Anatomy 0.000 description 1
• 229960000311 ritonavir Drugs 0.000 description 1
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
• 229960001852 saquinavir Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 150000003354 serine derivatives Chemical class 0.000 description 1
• 230000000697 serotonin reuptake Effects 0.000 description 1
• VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
• 229960002073 sertraline Drugs 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 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
• 235000013874 shellac Nutrition 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 210000001013 sinoatrial node Anatomy 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 230000000153 supplemental effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 206010042772 syncope Diseases 0.000 description 1
• 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960003080 taurine Drugs 0.000 description 1
• UISARWKNNNHPGI-UHFFFAOYSA-N terodiline Chemical compound C=1C=CC=CC=1C(CC(C)NC(C)(C)C)C1=CC=CC=C1 UISARWKNNNHPGI-UHFFFAOYSA-N 0.000 description 1
• 229960005383 terodiline Drugs 0.000 description 1
• IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 125000005259 triarylamine group Chemical group 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• ISNYUQWBWALXEY-OMIQOYQYSA-N tsg6xhx09r Chemical compound O([C@@H](C)C=1[C@@]23CN(C)CCO[C@]3(C3=CC[C@H]4[C@]5(C)CC[C@@](C4)(O)O[C@@]53[C@H](O)C2)CC=1)C(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-OMIQOYQYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 229940072690 valium Drugs 0.000 description 1
• 229960003726 vasopressin Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 1
• 229920006163 vinyl copolymer Polymers 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1