IE912237A1 - Pharmaceutical preparations - Google Patents
Pharmaceutical preparationsInfo
- Publication number
- IE912237A1 IE912237A1 IE223791A IE223791A IE912237A1 IE 912237 A1 IE912237 A1 IE 912237A1 IE 223791 A IE223791 A IE 223791A IE 223791 A IE223791 A IE 223791A IE 912237 A1 IE912237 A1 IE 912237A1
- Authority
- IE
- Ireland
- Prior art keywords
- receptor
- pharmaceutical product
- active ingredients
- uptake inhibitor
- product according
- Prior art date
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 229940127557 pharmaceutical product Drugs 0.000 claims abstract description 11
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 206010027599 migraine Diseases 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 208000020401 Depressive disease Diseases 0.000 claims abstract description 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 54
- 239000003112 inhibitor Substances 0.000 claims description 19
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 claims description 13
- 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 claims description 12
- 239000000018 receptor agonist Substances 0.000 claims description 12
- 229940044601 receptor agonist Drugs 0.000 claims description 12
- 239000000556 agonist Substances 0.000 claims description 6
- 229940044551 receptor antagonist Drugs 0.000 claims description 5
- 239000002464 receptor antagonist Substances 0.000 claims description 5
- 239000005557 antagonist Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical group CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims description 4
- 229960003708 sumatriptan Drugs 0.000 claims description 4
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 3
- 102000035037 5-HT3 receptors Human genes 0.000 claims description 3
- 108091005477 5-HT3 receptors Proteins 0.000 claims description 3
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims description 3
- 229960002296 paroxetine Drugs 0.000 claims description 3
- WIQRCHMSJFFONW-HNNXBMFYSA-N (3s)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound O([C@@H](CCN)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 WIQRCHMSJFFONW-HNNXBMFYSA-N 0.000 claims description 2
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 claims description 2
- 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 claims description 2
- FWYRGHMKHZXXQX-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-2-(dimethylamino)-2-methylpropan-1-ol Chemical compound CN(C)C(C)(CO)CC1=CC=C(Cl)C(Cl)=C1 FWYRGHMKHZXXQX-UHFFFAOYSA-N 0.000 claims description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 claims description 2
- 229950000303 cericlamine Drugs 0.000 claims description 2
- 229950001408 cianopramine Drugs 0.000 claims description 2
- LQXYCDLHSKICDY-UHFFFAOYSA-N cianopramine Chemical compound C1CC2=CC=C(C#N)C=C2N(CCCN(C)C)C2=CC=CC=C21 LQXYCDLHSKICDY-UHFFFAOYSA-N 0.000 claims description 2
- 229960001653 citalopram Drugs 0.000 claims description 2
- 229960004606 clomipramine Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229950003930 femoxetine Drugs 0.000 claims description 2
- OJSFTALXCYKKFQ-YLJYHZDGSA-N femoxetine Chemical compound C1=CC(OC)=CC=C1OC[C@@H]1[C@@H](C=2C=CC=CC=2)CCN(C)C1 OJSFTALXCYKKFQ-YLJYHZDGSA-N 0.000 claims description 2
- 229960002464 fluoxetine Drugs 0.000 claims description 2
- 229960004038 fluvoxamine Drugs 0.000 claims description 2
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 claims description 2
- 229950006314 ifoxetine Drugs 0.000 claims description 2
- ZHFIAFNZGWCLHU-YPMHNXCESA-N ifoxetine Chemical compound CC1=CC=CC(O[C@@H]2[C@@H](CNCC2)O)=C1C ZHFIAFNZGWCLHU-YPMHNXCESA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229950000319 seproxetine Drugs 0.000 claims description 2
- 229960002073 sertraline Drugs 0.000 claims description 2
- 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 claims description 2
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 6
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 230000002460 anti-migrenic effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- KYQBGUPALRZQEE-XZPOUAKSSA-N 3,3-dimethyl-n-[(1r,5s)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]-2h-indole-1-carboxamide;hydrochloride Chemical compound Cl.C1C(C)(C)C2=CC=CC=C2N1C(=O)NC(C1)C[C@H]2CC[C@@H]1N2C KYQBGUPALRZQEE-XZPOUAKSSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 2
- 229960003727 granisetron Drugs 0.000 description 2
- 239000008187 granular material Substances 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
- 238000002156 mixing Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 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
- 229920002134 Carboxymethyl cellulose Polymers 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-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- QYZRTBKYBJRGJB-PCMHIUKPSA-N Granisetron hydrochloride Chemical compound Cl.C1=CC=C2C(C(=O)NC3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 QYZRTBKYBJRGJB-PCMHIUKPSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- -1 colourants Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 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
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A pharmaceutical product comprising two or three active ingredients as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
Description
PHARMACEUTICAL PREPARATIONS The present invention relates to pharmaceutical preparations having antidepressant and/or antimigraine activity.
It has now been found that a combination of two or three active agents having different mechanism of action with respect to 5-HT (5-hydroxytryptamine) has good antidepressant and/or antimigraine activity. The effectiveness of the combination is potentially greater than could be predicted from a consideration of the activities of the individual components and it appears that a synergistic effect is being produced.
Accordingly, the present invention provides a pharmaceutical product comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HTreceptor agonist, as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
Suitable combinations are as follows: -ΗΤβ antagonist + 5-HT re-uptake inhibitor; -ΗΤβ antagonist + 5-HTj agonist; -HTj agonist + 5-HT re-uptake inhibitor; and -ΗΤβ antagonist + 5-HT re-uptake inhibitor + 5-HTagonist.
Suitable examples of 5-HT3 receptor antagonists are as described in WO 89/04660 and WO 90/01996 (Beecham Group p.l.c.), in particular BRL 43694A (granisetron) BRL 46470A (Example 5 in EP-A-247266); ondansetron or LY 277359.
Other examples of 5-HT3 receptor antagonists are described in EP-A-410509 (Duphar International Research B.V.), EP-AIE 912237 B3010 -2420086 (Fujisawa Pharmaceutical Co., Ltd.), EP-A-403261 (Glaxo Group Limited), EP-A-405784 (Ono Pharmaceutical Co., Ltd.), EP-A-419397 (A/S Ferrosan), EP-A-417746 (G.O. Searle & Co.) and EP-A-407137 (Yoshitomi Pharmaceutical Industries Ltd.).
Suitable examples of 5-HT re-uptake inhibitors include the antidepressants, paroxetine and femoxetine (U.S. Patent No. 4007196), citalopram, sertraline, fluoxetine, clomipramine, fluvoxamine, cianopramine, ifoxetine, cericlamine, SL 810385 (Synthelabo) and seproxetine.
Suitable examples of 5-HT-^ receptor agonists include those compounds described in GB 2035310A; GB 2124210A; EP-A-145459; GB 2150932; EP-A-147107; GB 2185020A; EP-A-303506; EP-A-303507; EP-A-354777; EP-A-254433; and GB 2162522A (Glaxo Group Limited) in particular the compound GR 43175 (sumatriptan) or GR 85548; and EP-A-313397 (The Wellcome Foundation Limited).
Information with respect to structure and activity of the specific compounds listed hereinbefore may be obtained from well known pharmaceutical industry references, such as Pharmaprojects, PJB publications Limited, Richmond, Surrey, U.K.
In a preferred aspect, the active components of the product are administered simultaneously although they may be administered separately e.g. the 5-HT3 antagonist administered first.
The present invention further provides a pharmaceutical composition comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist in combination with a B3010 -3pharmaceutically acceptable carrier.
The invention yet further provides the use of two or three active ingredients selected from a 5-HT 3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-^ receptor agonist in the manufacture of a pharmaceutical preparation for simultaneous, separate or sequential use in depression and/or migraine therapy.
The product of the invention may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule for either separate, sequential or simultaneous administration.
However, they may be adapted for other modes of administration, for example parenteral administration.
Other alternative modes of administration include sublingual or transdermal administration.
Generally, compositions containing from about 2.5 to 15 mg of granisetron or 0.01 to 10 mg of BRL 46470A, 10-50 mg of paroxetine and 10-50 mg sumatriptan in a ratio of around 1:4:4 are effective, but this will depend on the activity of the 5-HT3 receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HTagonist.
In order to obtain consistency of administration it is preferred that a composition of the invention is in the form of a unit-dose. Suitable unit dose forms include tablets, capsules and powders in sachets or vials. Such unit dose forms may contain a total of from 0.01 to 100 mg of a 5-ΗΤβ receptor antagonist and more usually from 0.5 to 50 mg, for example 0.5 to 25 mg such as 0.5, 1, 2, 3, 5, 10, 15 or 20 mg. The unit dose form will normally contain from about 5 to 100 mg of the 5-HT re-uptake inhibitor and/or 5 to 100 mg of the 5-HTi agonist, more usually 10 to 50 mg, for example B3010 -410, 15, 20, 25, 30 mg. Such compositions may be administered from 1 to 6 times a day, more usually from 2 to 4 times a day, in a manner such that the daily dose of 5-ΗΤ3 receptor antagonist is from 0.5 to 200 mg for a 70 kg human adult and more particularly from 0.5 to 25 mg, and the daily dose of the 5-HT re-uptake inhibitor and/or 5-HT^ agonist, is from 10 to 500 mg for a 70 kg human adult and more particularly from 10 to 100 mg.
With the above indicated dosage range, no adverse toxicological effects are indicated with the composition of the invention.
The compositions of the invention may be formulated with conventional excipients, such as a filler, a disintegrating agent, a binder, a lubricant, a flavouring agent. They are formulated in conventional manner, for example in a manner similar to that used for anti-hypertensive agents.
It is greatly preferred that the 5-HT3 receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HT·^ receptor agonist, are administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories. Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional B3010 -5excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents. The tablets may be coated according to well known methods in the art.
Suitable fillers for use include cellulose, mannitol, lactose and other similar agents. Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
These solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl β-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
B3010 -6Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
For parenteral administration, fluid unit dose forms are prepared containing a compound of the present invention and a sterile vehicle. The compound, depending on the vehicle and the concentration, can be either suspended or dissolved. Parenteral solutions are normally prepared by dissolving the io compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
Advantageously, adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum.
Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
As is common practice, the compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
It will be appreciated that each component of the product of the invention may be administered by a different route.
The present invention yet further provides a method of treating depression and/or migraine in mammals including man, which comprises administering to the suffering mammal an effective amount of a pharmaceutical composition B3010 -7comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist, in combination with a pharmaceutically acceptable carrier.
Standard methods for assessing 5-HT 3 receptor antagonist activity, 5-HT·^ receptor agonist activity and 5-HT re-uptake inhibition activity are known in the art, and are, for example, described or referenced in the aforementioned patent publication references.
Antidepressant and/or antimigraine activity is assessed in appropriate animal models for determining such activities and in appropriate clinical trial methods.
Claims (13)
1. A pharmaceutical product comprising two or three active ingredients selected from a 5-HT3 receptor 5 antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist, as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine. 10
2. A pharmaceutical product according to claim 1 comprising two active ingredients which are a 5-HT3 receptor antagonist and a 5-HT re-uptake inhibitor.
3. A pharmaceutical product according to claim 1 15 comprising two active ingredients which are a 5-HT3 receptor antagonist and a 5-HT-^ receptor agonist.
4. A pharmaceutical product according to claim 1 comprising two active ingredients which are a 5-HT| receptor 20 agonist and a 5-HT re-uptake inhibitor.
5. A pharmaceutical product according to claim 1 comprising three active ingredients which are a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT·^ 25 receptor agonist.
6. A pharmaceutical product according to claim 1 wherein a 5-HT3 receptor antagonist is selected from those described in WO 89/04660 and WO 90/01996.
7. A pharmaceutical product according to claim 1 wherein a 5-HT re-uptake inhibitor is selected from paroxetine, femoxetine, citalopram, sertraline, fluoxetine, clomipramine, fluvoxamine, cianopramine, ifoxetine, 35 cericlamine, SL 810385 and seproxetine. B3010 -98. A pharmaceutical product according to claim 1 wherein the 5-HT| receptor agonist is sumatriptan.
8. 9. A pharmaceutical composition comprising two or three 5 active ingredients selected from a 5-HT 3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist in combination with a pharmaceutically acceptable carrier.
9. 10
10. The use of two or three active ingredients selected from a 5-ΗΤβ receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist in the manufacture of a pharmaceutical preparation for simultaneous, separate or sequential use in depression and/or migraine therapy.
11. A pharmaceutical product according to claim 1, substantially as hereinbefore described.
12. A pharmaceutical composition according to claim 9, substantially as hereinbefore described.
13. Use according to claim 10, substantially as hereinbefore described.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909014364A GB9014364D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB909014367A GB9014367D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB909014365A GB9014365D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB909014354A GB9014354D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE912237A1 true IE912237A1 (en) | 1992-01-01 |
Family
ID=27450525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE223791A IE912237A1 (en) | 1990-06-28 | 1991-06-26 | Pharmaceutical preparations |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU8072691A (en) |
| IE (1) | IE912237A1 (en) |
| WO (1) | WO1992000103A1 (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5589511A (en) * | 1990-08-13 | 1996-12-31 | Sepracor Inc. | Method for treating migraine headaches using optically pure S(+) fluoxetine |
| DE4314976C1 (en) * | 1993-05-06 | 1994-10-06 | Lohmann Therapie Syst Lts | Transdermal therapeutic systems for the administration of drugs, process for their production and their use |
| AU5966196A (en) * | 1995-06-08 | 1997-01-09 | Eli Lilly And Company | Methods of treating cold and allergic rhinitis |
| ES2208870T3 (en) * | 1996-02-15 | 2004-06-16 | Janssen Pharmaceutica N.V. | USE OF 5HT4 RECEIVER ANTAGONISTS TO RESOLVE THE GASTROINTESTINAL EFFECTS OF SEROTONINE REABSORTION INHIBITORS. |
| AU739261B2 (en) | 1997-07-01 | 2001-10-11 | Pfizer Inc. | Sertraline salts and sustained-release dosage forms of sertraline |
| AU3891299A (en) * | 1998-05-21 | 1999-12-06 | Eli Lilly And Company | Combination therapy for treatment of depression |
| US6960577B2 (en) | 1998-05-22 | 2005-11-01 | Eli Lilly And Company | Combination therapy for treatment of refractory depression |
| AU761510B2 (en) * | 1998-05-22 | 2003-06-05 | Eli Lilly And Company | Combination therapy for treatment of refractory depression |
| WO1999061014A2 (en) * | 1998-05-28 | 1999-12-02 | Sepracor Inc. | Compositions and methods employing r(-) fluoxetine and other active ingredients |
| EP0966967A3 (en) * | 1998-05-29 | 2000-05-31 | Eli Lilly And Company | Combination therapy of olanzapine (zyprexa) and fluoxetine (prozac) for treatment of bipolar disorder |
| US20020107244A1 (en) * | 2001-02-02 | 2002-08-08 | Howard Harry R. | Combination treatment for depression |
| US7034059B2 (en) | 2001-07-02 | 2006-04-25 | Sepracor Inc. | Methods of using norfluoxetine |
| ES2426915T3 (en) | 2003-09-10 | 2013-10-25 | Brentwood Equities Ltd. | Diastereoisomers of 4-aryloxy-3-hydroxypiperidines |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3872872T2 (en) * | 1987-11-14 | 1993-02-04 | Beecham Group Plc | 5-HT3 RECEPTOR ANTAGONISTS FOR TREATMENT OF CUSHION AND BRONCHO CONSTRUCTION. |
-
1991
- 1991-06-20 AU AU80726/91A patent/AU8072691A/en not_active Abandoned
- 1991-06-20 WO PCT/GB1991/000992 patent/WO1992000103A1/en unknown
- 1991-06-26 IE IE223791A patent/IE912237A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992000103A1 (en) | 1992-01-09 |
| AU8072691A (en) | 1992-01-23 |
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