Zotepine

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Atypical antipsychotic medication

title: "Zotepine" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["alpha-2-blockers", "atypical-antipsychotics", "chloroarenes", "dibenzothiepines", "dimethylamino-compounds", "m1-receptor-antagonists", "m2-receptor-antagonists", "m3-receptor-antagonists", "m4-receptor-antagonists", "m5-receptor-antagonists", "norepinephrine-reuptake-inhibitors", "enol-ethers"] description: "Atypical antipsychotic medication" topic_path: "general/alpha-2-blockers" source: "https://en.wikipedia.org/wiki/Zotepine" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Atypical antipsychotic medication ::

| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 477869681 | IUPAC_name = 2-(3-chlorobenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethylethanamine | image = Zotepine skeletal formula based on 3D.svg | image_class = skin-invert-image | width = 220px | image2 = Zotepine-optimized-ball-and-stick.png | image_class2 = bg-transparent | width2 = 250px

| tradename = Zoleptil | Drugs.com = | pregnancy_category = | legal_AU = | legal_BR = C1 | legal_BR_comment = | legal_CA = | legal_DE = | legal_NZ = | legal_UK = | legal_US = | legal_EU = | legal_UN = | legal_status = Rx-only | routes_of_administration = Oral

| bioavailability = 7–13% (oral) | metabolism = N-desmethylation to norzotepine (30-40%) | elimination_half-life = 13.7–15.9 hours, 12 hours (Norzotepine) | excretion = 17% (Urine)

| CAS_number_Ref = | CAS_number = 26615-21-4 | ATC_prefix = N05 | ATC_suffix = AX11 | PubChem = 5736 | IUPHAR_ligand = 103 | DrugBank_Ref = | DrugBank = DB09225 | ChemSpiderID_Ref = | ChemSpiderID = 5534 | UNII_Ref = | UNII = U29O83JAZW | KEGG_Ref = | KEGG = D01321 | ChEBI_Ref = | ChEBI = 32316 | ChEMBL_Ref = | ChEMBL = 285802 | PDB_ligand = ZOT | synonyms =

| C=18 | H=18 | Cl=1 | N=1 | O=1 | S=1 | SMILES = Clc2cc1C(/OCCN(C)C)=C\c3c(Sc1cc2)cccc3 | StdInChI_Ref = | StdInChI = 1S/C18H18ClNOS/c1-20(2)9-10-21-16-11-13-5-3-4-6-17(13)22-18-8-7-14(19)12-15(16)18/h3-8,11-12H,9-10H2,1-2H3 | StdInChIKey_Ref = | StdInChIKey = HDOZVRUNCMBHFH-UHFFFAOYSA-N

Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 (although it has been discontinued in Germany) and Japan since 1982.

Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand.

Medical uses

Zotepine's primary use is as a treatment for schizophrenia although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania. In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, zotepine demonstrated medium-strong effectivity. Less effective than clozapine, slightly less effective than olanzapine and risperidone, approximately as effective as paliperidone, and slightly more effective than haloperidol, quetiapine, and aripiprazole.

Side effects

; Common

;Unknown frequency

;Rare

Pharmacology

Pharmacodynamics

The antipsychotic effect of zotepine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Zotepine has a high affinity for the D1 and D2 receptors. It also affects the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors. In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor.

::data[format=table]

Macromolecule (Receptor or transporter protein)Ki [nM]
SERT151
NET530
DAT3621
5-HT1A470.5
5-HT1B59.5
5-HT1D119
5-HT1E700
5-HT2A2.7
5-HT2C2.6
5-HT3472
5-HT5A29
5-HT66
5-HT712
α1A7
α1B5
α2A180
α2B5.35
α2C106
M118
M2140
M373
M477
M5260
D171
D225
D2S5.4
D2L11
D36.4
D418
D5248
H13.21
H2500
H41977
::

Synthesis

:[[File:Zotepine synthesis Fujisawa.svg|class=skin-invert-image|upright=2]] The reaction of 2-chloroacetophenone with 4-chlorothiophenol gives a thioether. This is treated with morpholine and sulfur in a Willgerodt–Kindler reaction to give a phenylacetic acid derivative after acid hydrolysis of the amide intermediate. Cyclization of this compound in the presence of polyphosphoric acid forms the dibenzothiepin ring system of the drug. The enol ether, zotepine, is produced when this is treated with the chloroethyl amine and potassium carbonate in methyl isobutyl ketone as solvent. Under these conditions, the undesired product of C-alkylation is minimised.

Society and culture

Brand names

Brand names include Losizopilon (JP), Lodopin (ID, JP), Nipolept (DE†), Setous (JP), Zoleptil (CZ, PT, TR, UK†), Zotewin (IN); where † indicates a formulation that has been discontinued.

References

References

  1. Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
  2. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  3. (16 August 2013). "Zotepine". Royal Pharmaceutical Society of Great Britain.
  4. (April 2010). "A single-blind, comparative study of zotepine versus haloperidol in combination with a mood stabilizer for patients with moderate-to-severe mania". Psychiatry and Clinical Neurosciences.
  5. (1986). "Antimanic effect of zotepine". Clinical Therapeutics.
  6. (October 2005). "Zotepine loading in acute and severely manic patients: a pilot study". Bipolar Disorders.
  7. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet.
  8. British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
  9. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet.
  10. National Institute of Mental Health. (12 January 2011). "PDSD Ki Database". University of North Carolina.
  11. (June 2010). "Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake". The Journal of Pharmacology and Experimental Therapeutics.
  12. (October 1975). "The synthesis of 10-(4-methylpiperazino)dibenzo (b,f)thiepin and related compounds. Neurotropic and psychotropic agents". Chemical & Pharmaceutical Bulletin.
  13. (October 1978). "Synthesis and pharmacological properties of 8-chloro-10-(2-dimethylaminoethoxy)dibenzo[b,f]thiepin and related compounds. Neurotropic and psychotropic agents. III". Chemical & Pharmaceutical Bulletin.
  14. "Zotepine". Thieme.

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alpha-2-blockersatypical-antipsychoticschloroarenesdibenzothiepinesdimethylamino-compoundsm1-receptor-antagonistsm2-receptor-antagonistsm3-receptor-antagonistsm4-receptor-antagonistsm5-receptor-antagonistsnorepinephrine-reuptake-inhibitorsenol-ethers