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Chlorprothixene (Cloxan, Taractan, Truxal) is a typical antipsychotic drug of the thioxanthene class and was the first of the series to be synthesized.[1] It was introduced in 1959 by Lundbeck.[2]
Pharmacology
Chlorprothixene exerts strong antagonism at the following receptors:
- 5-HT2: antipsychotic effects, anxiolysis, weight gain
- D1, D2, D3: antipsychotic effects, sedation, extrapyramidal side effects, prolactin increase, depression, apathy/anhedonia, weight gain
- H1: sedation, weight gain
- mACh: anticholinergic effects, inhibition of extrapyramidal side effects
- α1-adrenergic: hypotension, tachycardia
Indications
Chlorprothixene's principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occurring as part of bipolar disorders.
Other uses are pre- and postoperative states with anxiety and insomnia, severe nausea / emesis (in hospitalized patients), the amelioration of anxiety and agitation due to use of selective serotonin reuptake inhibitors for depression and, off-label, the amelioration of alcohol and opioid withdrawal. It may also be used cautiously to treat nonpsychotic irritability, aggression, and insomnia in pediatric patients.
An intrinsic antidepressant effect of chlorprothixene has been discussed, but not proven yet. Likewise, it is unclear, if chlorprothixene has genuine (intrinsic) analgesic effects. However, chlorprothixene can be used as comedication in severe chronic pain. Also, like most antipsychotics, chlorprothixene has antiemetic effects.
Side effects
Chlorprothixene has a strong sedative activity with a high incidence of anticholinergic side effects. The types of side effects encountered (dry mouth, massive hypotension and tachycardia, hyperhidrosis, substantial weight gain etc.) normally do not allow a full effective dose for the remission of psychotic disorders to be given. So cotreatment with another, more potent, antipsychotic agent is needed.
Chlorprothixene is structurally related to chlorpromazine, with which it shares in principal all side effects. Allergic side effects and liver damage seem to appear with an appreciable lower frequency. The elderly are particularly sensitive to anticholinergic side effects of chlorprothixene (precipitation of narrow angle glaucoma, severe obstipation, difficulties in urinating, confusional and delirant states). In patients >60 years the doses should be particularly low.
Early and late extrapyramidal side effects may occur but have been noted with a low frequency (one study with a great number of participants has delivered a total number of only 1%).
Dosage
The initial doses of chlorprothixene should always be as low as possible (e.g. 30 mg at bedtime, 15 mg morning dose) and be increased gradually. Patients receiving 90 mg daily (and more) of the drug should be hospitalized, particularly during the initial phase of treatment. The theoretical maximum is 800 mg daily which can usually not be given due to side effects as stated above. Elderly and pediatric patients should be treated with particular low initial doses. Dose increments should be done slowly. If chlorprothixene is to be withdrawn, it should not be stopped abruptly, but the dose should be decreased steadily.
Interactions
Chlorprothixene may increase the plasma-level of concomitantly given lithium. In order to avoid lithium intoxication, lithium plasma levels should be monitored closely.
If chlorprothixene is given concomitantly with opioids, the opioid dose should be reduced (by approx. 50%), because chlorprothixene amplifies the therapeutic actions and side effects of opioids considerably.
Avoid the concomitant use of chlorprothixene and tramadol (Ultram). Massive seizures may be encountered with this combination.
Consider additive sedative effects and confusional states to emerge, if chlorprothixene is given with benzodiazepines or barbiturates. Choose particular low doses of these drugs.
Exert particular caution in combining chlorprothixene with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even ileus and glaucoma .
See also
References
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| Agonists: 5-FNE • 6-FNE • Amidephrine • Anisodamine • Anisodine • Cirazoline • Dipivefrine • Dopamine • Ephedrine • Epinephrine (Adrenaline) • Etilefrine • Ethylnorepinephrine • Indanidine • Levonordefrin • Metaraminol • Methoxamine • Methyldopa • Midodrine • Naphazoline • Norepinephrine (Noradrenaline) • Octopamine • Oxymetazoline • Phenylephrine • Phenylpropanolamine • Pseudoephedrine • Synephrine • TetrahydrozolineAntagonists: Abanoquil • Adimolol • Ajmalicine • Alfuzosin • Amosulalol • Arotinolol • Atiprosin • Benoxathian • Buflomedil • Bunazosin • Carvedilol • CI-926 • Corynanthine • Dapiprazole • DL-017 • Domesticine • Doxazosin • Eugenodilol • Fenspiride • GYKI-12,743 • GYKI-16,084 • Indoramin • Ketanserin • L-765,314 • Labetalol • Mephendioxan • Metazosin • Monatepil • Moxisylyte (Thymoxamine) • Naftopidil • Nantenine • Neldazosin • Nicergoline • Niguldipine • Pelanserin • Phendioxan • Phenoxybenzamine • Phentolamine • Piperoxan • Prazosin • Quinazosin • Ritanserin • RS-97,078 • SGB-1,534 • Silodosin • SL-89.0591 • Spiperone • Talipexole • Tamsulosin • Terazosin • Tibalosin • Tiodazosin • Tipentosin • Tolazoline • Trimazosin • Upidosin • Urapidil • Zolertine* Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole all antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension. |
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| Agonists: 77-LH-28-1 • AC-42 • AC-260,584 • Aceclidine • Acetylcholine • AF30 • AF150(S) • AF267B • AFDX-384 • Alvameline • AQRA-741 • Arecoline • Bethanechol • Butyrylcholine • Carbachol • CDD-0034 • CDD-0078 • CDD-0097 • CDD-0098 • CDD-0102 • Cevimeline • cis-Dioxolane • Ethoxysebacylcholine • LY-593,039 • L-689,660 • LY-2,033,298 • McNA343 • Methacholine • Milameline • Muscarine • NGX-267 • Ocvimeline • Oxotremorine • PD-151,832 • Pilocarpine • RS86 • Sabcomeline • SDZ 210-086 • Sebacylcholine • Suberylcholine • Talsaclidine • Tazomeline • Thiopilocarpine • Vedaclidine • VU-0029767 • VU-0090157 • VU-0152099 • VU-0152100 • VU-0238429 • WAY-132,983 • Xanomeline • YM-796Antagonists: 3-Quinuclidinyl Benzilate • 4-DAMP • Aclidinium Bromide • Anisodamine • Anisodine • Atropine • Atropine Methonitrate • Benactyzine • Benzatropine (Benztropine) • Benzydamine • BIBN 99 • Biperiden • Bornaprine • CAR-226,086 • CAR-301,060 • CAR-302,196 • CAR-302,282 • CAR-302,368 • CAR-302,537 • CAR-302,668 • CS-27349 • Cyclobenzaprine • Cyclopentolate • Darifenacin • DAU-5884 • Dimethindene • Dexetimide • DIBD • Dicyclomine (Dicycloverine) • Ditran • EA-3167 • EA-3443 • EA-3580 • EA-3834 • Elemicin • Etanautine • Etybenzatropine (Ethylbenztropine) • Flavoxate • Himbacine • HL-031,120 • Ipratropium • J-104,129 • Hyoscyamine • Mamba Toxin 3 • Mamba Toxin 7 • Mazaticol • Mebeverine • Methoctramine • Metixene • Myristicin • N-Ethyl-3-Piperidyl Benzilate • N-Methyl-3-Piperidyl Benzilate • Orphenadrine • Otenzepad • Oxybutynin • PBID • PD-102,807 • Phenglutarimide • Phenyltoloxamine • Pirenzepine • Piroheptine • Procyclidine • Profenamine • RU-47,213 • SCH-57,790 • SCH-72,788 • SCH-217,443 • Scopolamine (Hyoscine) • Solifenacin • Telenzepine • Tiotropium • Tolterodine • Trihexyphenidyl • Tripitamine • Tropatepine • Tropicamide • WIN-2299 • Xanomeline • Zamifenacin; Others: 1st Generation Antihistamines ( Brompheniramine, chlorpheniramine, cyproheptadine, dimenhydrinate, diphenhydramine, doxylamine, mepyramine/ pyrilamine, phenindamine, pheniramine, tripelennamine, triprolidine, etc) • Tricyclic Antidepressants ( Amitriptyline, doxepin, trimipramine, etc) • Tetracyclic Antidepressants ( Amoxapine, maprotiline, etc) • Typical Antipsychotics ( Chlorpromazine, thioridazine, etc) • Atypical Antipsychotics ( Clozapine, olanzapine, quetiapine, etc) |
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| Agonists: 5-HIAA • A-84,543 • A-366,833 • A-582,941 • A-867,744 • ABT-202 • ABT-418 • ABT-560 • ABT-894 • Acetylcholine • Altinicline • Anabasine • AR-R17779 • Butyrylcholine • Carbachol • Cotinine • Cytisine • Decamethonium • Desformylflustrabromine • Dianicline • Dimethylphenylpiperazinium • Epibatidine • Epiboxidine • Ethanol • Ethoxysebacylcholine • EVP-4473 • EVP-6124 • Galantamine • GTS-21 • Ispronicline • Lobeline • MEM-63,908 (RG-3487) • Nicotine • NS-1738 • PHA-543,613 • PHA-709,829 • PNU-120,596 • PNU-282,987 • Pozanicline • Rivanicline • Sazetidine A • Sebacylcholine • SIB-1508Y • SIB-1553A • SSR-180,711 • Suberylcholine • TC-1698 • TC-1734 • TC-1827 • TC-2216 • TC-5214 • TC-5619 • TC-6683 • Tebanicline • Tropisetron • UB-165 • Varenicline • WAY-317,538 • XY-4083Antagonists: 18-Methoxycoronaridine • α-Bungarotoxin • α-Conotoxin • Alcuronium • Amantadine • Anatruxonium • Atracurium • Bupropion (Amfebutamone) • Chandonium • Chlorisondamine • Cisatracurium • Coclaurine • Coronaridine • Dacuronium • Decamethonium • Dextromethorphan • Dextropropoxyphene • Dextrorphan • Diadonium • DHβE • Dimethyltubocurarine (Metocurine) • Dipyrandium • Dizocilpine (MK-801) • Doxacurium • Duador • Esketamine • Fazadinium • Gallamine • Hexafluronium • Hexamethonium (Benzohexonium) • Ibogaine • Isoflurane • Ketamine • Kynurenic acid • Laudexium (Laudolissin) • Levacetylmethadol • Malouetine • Mecamylamine • Memantine • Methadone • Methorphan (Racemethorphan) • Methyllycaconitine • Metocurine • Mivacurium • Morphanol (Racemorphanol) • Neramexane • Nitrous Oxide • Pancuronium • Pempidine • Pentamine • Pentolinium • Phencyclidine • Pipecuronium • Radafaxine • Rapacuronium • Rocuronium • Surugatoxin • Suxamethonium (Succinylcholine) • Thiocolchicoside • Toxiferine • Trimethaphan • Tropeinium • Tubocurarine • Vecuronium • Xenon |
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| * Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors. |
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| Adamantanes: Amantadine • Memantine • Rimantadine; Aminotetralins: 7-OH-DPAT • 8-OH-PBZI • Rotigotine • UH-232; Benzazepines: 6-Br-APB • Fenoldopam • SKF-38,393 • SKF-77,434 • SKF-81,297 • SKF-82,958 • SKF-83,959; Ergolines: Bromocriptine • Cabergoline • Dihydroergocryptine • Lisuride • LSD • Pergolide; Dihydrexidine derivatives: 2-OH-NPA • A-86,929 • Ciladopa • Dihydrexidine • Dinapsoline • Dinoxyline • Doxanthrine; Others: A-68,930 • A-77,636 • A-412,997 • ABT-670 • ABT-724 • Aplindore • Apomorphine • Aripiprazole • Bifeprunox • BP-897 • CY-208,243 • Dizocilpine • Etilevodopa • Flibanserin • Ketamine • Melevodopa • Modafinil • Pardoprunox • Phencyclidine • PD-128,907 • PD-168,077 • PF-219,061 • Piribedil • Pramipexole • Propylnorapomorphine • Pukateine • Quinagolide • Quinelorane • Quinpirole • RDS-127 • Ro10-5824 • Ropinirole • Rotigotine • Roxindole • Salvinorin A • SKF-89,145 • Sumanirole • Terguride • Umespirone • WAY-100,635 |
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Morpholines: Fenbutrazate • Morazone • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-CAB • 4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • Alfetamine • Amfecloral • Amfepentorex • Amfepramone • Amphetamine ( Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • Benzphetamine • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • D-Deprenyl • Dimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, metamfepramone) • Ethcathinone (Ethylpropion) • Ethylamphetamine • Ethylbenzodioxolylbutanamine (EBDB) • Ethylone • Famprofazone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • Lophophine (Homomyristicylamine) • Mefenorex • Mephedrone • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • Methedrone • Methoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA, tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA, homarylamine) • Methylenedioxyphenethylamine (MDPEA, homopiperonylamine) • Methylone • Ortetamine • Parabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paredrine (Norpholedrine, Oxamphetamine) • Phenethylamine (PEA) • Pholedrine • Phenpromethamine • Prenylamine • Propylamphetamine • Tiflorex (Flutiorex) • Tyramine (TRA) • Xylopropamine • Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP, paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP, piperonylpiperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN) • 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 4-Benzylpiperidine (4-BP) • 5-IAI • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanylaminopropane (IAP) • Indanorex • Isometheptene • Methylhexanamine • Naphthylaminopropane (NAP) • Octodrine • Phthalimidopropiophenone • Propylhexedrine ( Levopropylhexedrine) • Tuaminoheptane (Tuamine) |
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Receptor
ligands | | Agonists: 2-Pyridylethylamine • Betahistine • Histamine • HTMT • UR-AK49Antagonists: 1st generation: 4-Methyldiphenhydramine • Alimemazine • Antazoline • Azatadine • Bamipine • Benzatropine (Benztropine) • Bepotastine • Bromazine • Brompheniramine • Buclizine • Captodiame • Carbinoxamine • Chlorcyclizine • Chloropyramine • Chlorothen • Chlorpheniramine • Chlorphenoxamine • Cinnarizine • Clemastine • Clobenzepam • Clocinizine • Cyclizine • Cyproheptadine • Dacemazine • Deptropine • Dexbrompheniramine • Dexchlorpheniramine • Dimenhydrinate • Dimetindene • Diphenhydramine • Diphenylpyraline • Doxylamine • Embramine • Etybenzatropine (Ethylbenztropine) • Etymemazine • Histapyrrodine • Homochlorcyclizine • Hydroxyethylpromethazine • Hydroxyzine • Isopromethazine • Isothipendyl • Meclozine • Mepyramine (Pyrilamine) • Mequitazine • Methafurylene • Methapyrilene • Methdilazine • Moxastine • Niaprazine • Orphenadrine • Oxatomide • Oxomemazine • Phenindamine • Pheniramine • Phenyltoloxamine • Pimethixene • Piperoxan • Promethazine • Propiomazine • Pyrrobutamine • Talastine • Thenalidine • Thenyldiamine • Thiazinamium • Thonzylamine • Tolpropamine • Tripelennamine • Triprolidine; 2nd generation: Acrivastine • Astemizole • Azelastine • Cetirizine • Clemizole • Clobenztropine • Ebastine • Emedastine • Epinastine • Ketotifen • Latrepirdine • Levocabastine • Loratadine • Mebhydrolin • Mizolastine • Olopatadine • Rupatadine • Setastine • Terfenadine; 3rd generation: Desloratadine • Fexofenadine • Levocetirizine; Miscellaneous: Tricyclic Antidepressants ( Amitriptyline, Doxepin, Trimipramine, etc) • Tetracyclic Antidepressants ( Mianserin, Mirtazapine, etc) • Serotonin Antagonists and Reuptake Inhibitors ( Trazodone, Nefazodone) • Typical Antipsychotics ( Chlorpromazine, Thioridazine, etc) • Atypical Antipsychotics ( Clozapine, Olanzapine, Quetiapine, etc) |
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| Agonists: Azapirones: Alnespirone • Binospirone • Buspirone • Enilospirone • Eptapirone • Gepirone • Ipsapirone • Perospirone • Revospirone • Tandospirone • Tiospirone • Umespirone • Zalospirone; Antidepressants: Etoperidone • Nefazodone • Trazodone; Antipsychotics: Aripiprazole • Asenapine • Clozapine • Quetiapine • Ziprasidone; Ergolines: Dihydroergotamine • Ergotamine • Lisuride • Methysergide • LSD; Tryptamines: 5-CT • 5-MeO-DMT • 5-MT • Bufotenin • DMT • Psilocin • Psilocybin; Others: 8-OH-DPAT • Adatanserin • Befiradol • BMY-14802 • Cannabidiol • Dimemebfe • Ebalzotan • Eltoprazine • F-11,461 • F-12,826 • F-13,714 • F-14,679 • F-15,063 • F-15,599 • Flesinoxan • Flibanserin • Lesopitron • Lu AA21004 • LY-293,284 • LY-301,317 • MKC-242 • NBUMP • Osemozotan • Oxaflozane • Pardoprunox • Piclozotan • Rauwolscine • Repinotan • Roxindole • RU-24,969 • S 14,506 • S-14,671 • S-15,535 • Sarizotan • SSR-181,507 • Sunepitron • U-92016A • Urapidil • Vilazodone • Xaliproden • YohimbineAntagonists: Antipsychotics: Iloperidone • Risperidone • Sertindole; Beta blockers: Alprenolol • Cyanopindolol • Iodocyanopindolol • Oxprenolol • Pindobind • Pindolol • Propranolol • Tertatolol; Others: AV965 • BMY-7378 • CSP-2503 • Dotarizine • Flopropione • GR-46611 • Isamoltane • Lecozotan • Metitepine/Methiothepin • MPPF • NAN-190 • PRX-00023 • Robalzotan • S-15535 • SB-649915 • SDZ 216-525 • Spiperone • Spiramide • Spiroxatrine • UH-301 • WAY-100,135 • WAY-100,635 • Xylamidine |
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| Agonists: Lysergamides: Dihydroergotamine • Methysergide; Triptans: Almotriptan • Avitriptan • Eletriptan • Frovatriptan • Naratriptan • Rizatriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CP-135,807 • CP-286,601 • GR-46611 • L-694,247 • L-772,405 • PNU-109,291 • PNU-142,633Antagonists: Lysergamides: Metergoline; Others: Alniditan • BRL-15572 • Elzasonan • GR-127,935 • Ketanserin • LY-310,762 • LY-367,642 • LY-456,219 • LY-456,220 • Metitepine/Methiothepin • Ritanserin • Yohimbine • Ziprasidone |
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| Agonists: Phenethylamines: 2C-B • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline; Piperazines: Aripiprazole • mCPP • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: A-372,159 • AL-38022A • CP-809,101 • Dimemebfe • Lorcaserin• Medifoxamine • MK-212 • ORG-37,684 • Oxaflozane • PNU-22394 • Ro60-0175 • Vabicaserin • WAY-629 • WAY-161,503 • YM-348Antagonists: Atypical antipsychotics: Clozapine • Iloperidone • Melperone • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical antipsychotics: Chlorpromazine • Loxapine • Pipamperone; Antidepressants: Agomelatine • Amitriptyline • Amoxapine • Aptazapine • Etoperidone • Fluoxetine • Mianserin • Mirtazapine • Nefazodone • Nortriptyline • Trazodone; Others: Adatanserin • Cinanserin • Cyproheptadine • Deramciclane • Dotarizine • Eltoprazine • Esmirtazapine • FR-260,010 • Ketanserin • Ketotifen • Latrepirdine • Lu AA24530 • Metitepine/Methiothepin • Methysergide • Pizotifen • Ritanserin • RS-102,221 • S-14,671 • SB-200,646 • SB-206,553 • SB-221,284 • SB-228,357 • SB-242,084 • SB-243,213 • SDZ SER-082 • Xylamidine |
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| Agonists: Lysergamides: Dihydroergotamine • Ergotamine • Lisuride • LSD • Mesulergine • Metergoline • Methysergide; Tryptamines: 2-Methyl-5-HT • 5-BT • 5-CT • 5-MT • Bufotenin • E-6801 • E-6837 • EMD-386,088 • EMDT • LY-586,713 • N-Methyl-5-HT • Tryptamine; Others: WAY-181,187 • WAY-208,466Antagonists: Antidepressants: Amitriptyline • Amoxapine • Clomipramine • Doxepin • Mianserin • Nortriptyline; Atypical antipsychotics: Aripiprazole • Asenapine • Clozapine • Fluperlapine • Iloperidone • Olanzapine • Tiospirone; Typical antipsychotics: Chlorpromazine • Loxapine; Others: BGC20-760 • BVT-5182 • BVT-74316 • EGIS-12233 • GW-742,457 • Ketanserin • Latrepirdine • Lu AE58054 • Metitepine/Methiothepin • MS-245 • PRX-07034 • Ritanserin • Ro 04-6790 • Ro 63-0563 • SB-258,585 • SB-271,046 • SB-357,134 • SB-399,885 • SB-742,457 |
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de:Chlorprothixen
fr:Chlorprothixène
hu:Klórprotixén
nl:Chloorprotixeen
pl:Chlorprotiksen
ru:Хлорпротиксен
fi:Klooriprotikseeni
sv:Klorprotixen
- ↑ Healy, David (1997). The antidepressant era. Cambridge: Harvard University Press. p. 182. ISBN 0-674-03958-0.
- ↑ Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 410. ISBN 0-471-89980-1.
