Peringatan Keamanan

The use of zotepine has been vastly related to ongoing extrapyramidal side effects and it has been reported to be poorly tolerated by the patients.A31855, A31857

Zotepine

DB09225

small molecule approved investigational withdrawn

Deskripsi

Zotepine, with the formula (2-chloro-11-(2-dimethyl-amino-ethoxy)-dibenzo thiepin, is a neuroleptic drug. It was designed and synthesized by Fujisawa Pharmaceutical Co Ltd.A31855 It has been used as an antipsychotic in Japan, India and some places in Europe like UK and Germany since 1980's.A31857 Zotepine was never approved by the FDA. In 1993, it was classified as inactive drug substance (Status I, Type II) and in 1995 the FDA studied the manufacturing procedures of Zotepine tablets in Germany, but the status remained inactive.L1082 When the analysis of antipsychotics was retaken in 2016 by the FDA, zotepine did not reach the threshold effect to be further studied.L1313. In the EMA, by 2015 it was under pharmacovigilance studies for the potential treatment of acute renal failure.L1314

Struktur Molekul 2D

Berat 331.86
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half-life of zotepine is reported to be of 21 hours.[A31893]
Volume Distribusi The apparent volume of distribution of zotepine is 109 L/kg.[A31893]
Klirens (Clearance) The apparent oral clearance of zotepine is 4.6 mg/h.kg.[A31893]

Absorpsi

Preclinical pharmacokinetic studies have shown a dose-dependent increase in plasma levels with a tmax between 2-4 hours and Cmax from 6.9-19.6 ng/ml when administered in a dose of 25-100 mg of zotepine. The maximum concentration peaks and slow declines thereafter.A31864 When administered orally in preclinical studies, zotepine was proven to be absorbed rapidly and almost completely from the gastrointestinal tract.The unchanged drug and metabolites are rapidly distributed to the tissues.A31892

Metabolisme

Zotepine is well metabolized in the body, it actually undergoes extensive first-pass metabolism to the metabolite norzotepine and several inactive metabolites. The main enzymes involved in zotepine metabolism are CYP1A2 and CYP3A4.L1341 Some of the main metabolic pathways include N-demethylation and oxygenation of N or S atoms, hydroxylation of the aromatic ring and consecutive conjugation.A31892

Rute Eliminasi

Only small amounts of the unchanged zotepine are excreted in the urine and fecal excretion through the bile is the main route of elimination of both the unchanged drug and its metabolites.A31892

Interaksi Obat

1076 Data
Deferasirox The serum concentration of Zotepine can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Zotepine can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Zotepine can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Zotepine can be decreased when it is combined with Teriflunomide.
Buprenorphine Zotepine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Hydrocodone Zotepine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Hydroxyzine Hydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Magnesium sulfate The therapeutic efficacy of Zotepine can be increased when used in combination with Magnesium sulfate.
Methotrimeprazine Zotepine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosine Zotepine may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Orphenadrine Zotepine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehyde Zotepine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Rotigotine Zotepine may increase the sedative activities of Rotigotine.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Zotepine.
Sodium oxybate Zotepine may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Suvorexant Zotepine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Thalidomide Zotepine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Zotepine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Amisulpride Zotepine may increase the antipsychotic activities of Amisulpride.
Methylphenidate The risk or severity of adverse effects can be increased when Zotepine is combined with Methylphenidate.
Metoclopramide The risk or severity of adverse effects can be increased when Metoclopramide is combined with Zotepine.
Quinagolide The therapeutic efficacy of Quinagolide can be decreased when used in combination with Zotepine.
Sulpiride Zotepine may increase the antipsychotic activities of Sulpiride.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Zotepine.
Lithium citrate Lithium citrate may increase the neurotoxic activities of Zotepine.
Lithium hydroxide Lithium hydroxide may increase the neurotoxic activities of Zotepine.
Mequitazine Zotepine may increase the arrhythmogenic activities of Mequitazine.
Linezolid The risk or severity of serotonin syndrome can be increased when Linezolid is combined with Zotepine.
Dicoumarol The risk or severity of adverse effects can be increased when Zotepine is combined with Dicoumarol.
Phenindione The risk or severity of adverse effects can be increased when Zotepine is combined with Phenindione.
Coumarin The risk or severity of adverse effects can be increased when Zotepine is combined with Coumarin.
Tioclomarol The risk or severity of adverse effects can be increased when Zotepine is combined with Tioclomarol.
Phenprocoumon The risk or severity of adverse effects can be increased when Zotepine is combined with Phenprocoumon.
4-hydroxycoumarin The risk or severity of adverse effects can be increased when Zotepine is combined with 4-hydroxycoumarin.
Ethyl biscoumacetate The risk or severity of adverse effects can be increased when Zotepine is combined with Ethyl biscoumacetate.
Fluindione The risk or severity of adverse effects can be increased when Zotepine is combined with Fluindione.
Clorindione The risk or severity of adverse effects can be increased when Zotepine is combined with Clorindione.
Diphenadione The risk or severity of adverse effects can be increased when Zotepine is combined with Diphenadione.
(S)-Warfarin The risk or severity of adverse effects can be increased when Zotepine is combined with (S)-Warfarin.
Abiraterone The serum concentration of Zotepine can be increased when it is combined with Abiraterone.
Mirtazapine Zotepine may increase the serotonergic activities of Mirtazapine.
Cyproterone acetate The metabolism of Zotepine can be increased when combined with Cyproterone acetate.
Ethanol Zotepine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Azelastine Zotepine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.
Zimelidine The risk or severity of adverse effects can be increased when Zotepine is combined with Zimelidine.
Dapoxetine The risk or severity of adverse effects can be increased when Zotepine is combined with Dapoxetine.
Seproxetine The risk or severity of adverse effects can be increased when Zotepine is combined with Seproxetine.
Citalopram The risk or severity of adverse effects can be increased when Zotepine is combined with Citalopram.
Duloxetine The risk or severity of adverse effects can be increased when Zotepine is combined with Duloxetine.
Paroxetine The risk or severity of adverse effects can be increased when Zotepine is combined with Paroxetine.
Sertraline The risk or severity of adverse effects can be increased when Zotepine is combined with Sertraline.
Sibutramine The risk or severity of adverse effects can be increased when Zotepine is combined with Sibutramine.
Milnacipran The risk or severity of adverse effects can be increased when Zotepine is combined with Milnacipran.
Desvenlafaxine The risk or severity of serotonin syndrome can be increased when Desvenlafaxine is combined with Zotepine.
Levomilnacipran The risk or severity of serotonin syndrome can be increased when Zotepine is combined with Levomilnacipran.
Indalpine The risk or severity of adverse effects can be increased when Zotepine is combined with Indalpine.
Ritanserin The risk or severity of adverse effects can be increased when Zotepine is combined with Ritanserin.
Alaproclate The risk or severity of adverse effects can be increased when Zotepine is combined with Alaproclate.
Carbidopa The therapeutic efficacy of Carbidopa can be decreased when used in combination with Zotepine.
Cabergoline The therapeutic efficacy of Cabergoline can be decreased when used in combination with Zotepine.
Tolcapone The therapeutic efficacy of Tolcapone can be decreased when used in combination with Zotepine.
Metixene The therapeutic efficacy of Metixene can be decreased when used in combination with Zotepine.
Trihexyphenidyl The therapeutic efficacy of Trihexyphenidyl can be decreased when used in combination with Zotepine.
Procyclidine The therapeutic efficacy of Procyclidine can be decreased when used in combination with Zotepine.
Profenamine The therapeutic efficacy of Profenamine can be decreased when used in combination with Zotepine.
Entacapone The therapeutic efficacy of Entacapone can be decreased when used in combination with Zotepine.
Lisuride The therapeutic efficacy of Lisuride can be decreased when used in combination with Zotepine.
Apomorphine The therapeutic efficacy of Apomorphine can be decreased when used in combination with Zotepine.
Biperiden The therapeutic efficacy of Biperiden can be decreased when used in combination with Zotepine.
Amantadine The therapeutic efficacy of Amantadine can be decreased when used in combination with Zotepine.
Memantine The therapeutic efficacy of Memantine can be decreased when used in combination with Zotepine.
Pergolide The therapeutic efficacy of Pergolide can be decreased when used in combination with Zotepine.
Levodopa The therapeutic efficacy of Levodopa can be decreased when used in combination with Zotepine.
3,5-Dinitrocatechol The therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Zotepine.
Etilevodopa The therapeutic efficacy of Etilevodopa can be decreased when used in combination with Zotepine.
Ifenprodil The therapeutic efficacy of Ifenprodil can be decreased when used in combination with Zotepine.
Dexetimide The therapeutic efficacy of Dexetimide can be decreased when used in combination with Zotepine.
Opicapone The therapeutic efficacy of Opicapone can be decreased when used in combination with Zotepine.
Piribedil The therapeutic efficacy of Piribedil can be decreased when used in combination with Zotepine.
Benserazide The therapeutic efficacy of Benserazide can be decreased when used in combination with Zotepine.
Tropatepine The therapeutic efficacy of Tropatepine can be decreased when used in combination with Zotepine.
Melevodopa The therapeutic efficacy of Melevodopa can be decreased when used in combination with Zotepine.
Dihydroergocryptine The therapeutic efficacy of Dihydroergocryptine can be decreased when used in combination with Zotepine.
Phenglutarimide The therapeutic efficacy of Phenglutarimide can be decreased when used in combination with Zotepine.
Mazaticol The therapeutic efficacy of Mazaticol can be decreased when used in combination with Zotepine.
Etybenzatropine The therapeutic efficacy of Etybenzatropine can be decreased when used in combination with Zotepine.
Budipine The therapeutic efficacy of Budipine can be decreased when used in combination with Zotepine.
Bornaprine The therapeutic efficacy of Bornaprine can be decreased when used in combination with Zotepine.
Etanautine The therapeutic efficacy of Etanautine can be decreased when used in combination with Zotepine.
Dexpramipexole The therapeutic efficacy of Dexpramipexole can be decreased when used in combination with Zotepine.
Bromocriptine The therapeutic efficacy of Bromocriptine can be decreased when used in combination with Zotepine.
Methylene blue Zotepine may increase the serotonergic activities of Methylene blue.

Target Protein

D(1) dopamine receptor DRD1
D(2) dopamine receptor DRD2
5-hydroxytryptamine receptor 2A HTR2A
5-hydroxytryptamine receptor 7 HTR7
Sodium-dependent noradrenaline transporter SLC6A2
Sodium-dependent serotonin transporter SLC6A4
5-hydroxytryptamine receptor 6 HTR6

Referensi & Sumber

Artikel (PubMed)
  • PMID: 6124648
    Satoh H, Shimomura K, Mori J: Effect of zotepine on afterdischarge induced by electrical stimulation of amygdaloid nucleus in rats. Jpn J Pharmacol. 1982 Apr;32(2):381-3.
  • PMID: 22174537
    Bishnoi RJ, Jhanwar VG: Tolerability of zotepine in Indian patients: Preliminary experience. Ind Psychiatry J. 2010 Jul;19(2):130-1. doi: 10.4103/0972-6748.90345.
  • PMID: 2883677
    Saletu B, Grunberger J, Linzmayer L, Anderer P: Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry. Pharmacopsychiatry. 1987 Feb;20(1 Spec No):12-27. doi: 10.1055/s-2007-1017125.
  • PMID: 1683340
    Saletu B, Grunberger J, Anderer P, Chwatal K: Relation between blood levels and average quantitative EEG and psychometrically assessed pharmacodynamic changes following zotepine. Fortschr Neurol Psychiatr. 1991 Sep;59 Suppl 1:45-55. doi: 10.1055/s-2007-1000735.
  • PMID: 42414
    Noda K, Suzuki A, Okui M, Noguchi H, Nishiura M, Nishiura N: Pharmacokinetics and metabolism of 2-chloro-11-(2-dimethylaminoethoxy)-dibenzob,fthiepine (zotepine) in rat, mouse, dog and man. Arzneimittelforschung. 1979;29(10):1595-600.
  • PMID: 9485566
    Tanaka O, Kondo T, Otani K, Yasui N, Tokinaga N, Kaneko S: Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects. Ther Drug Monit. 1998 Feb;20(1):117-9.
Textbook
  • Wright P. and O'Neill M. (2012). Core psychiatry (3rd ed.). Elsevier.
  • Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.

Contoh Produk & Brand

Produk: 0 • International brands: 2
International Brands
  • Losizopilon
  • Zoleptil

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