Zotepine

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
Clinical data
Trade namesZoleptil
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability7–13% (oral)[1]
MetabolismN-desmethylation to norzotepine (30-40%)[1]
Elimination half-life13.7–15.9 hours, 12 hours (Norzotepine)[1]
Excretion17% (Urine)[1]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.189.143
Chemical and physical data
FormulaC18H18ClNOS
Molar mass331.86 g·mol−1
3D model (JSmol)
 NY (what is this?)  (verify)

Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand.[2]

Medical uses

Zotepine's primary use is as a treatment for schizophrenia[3] although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania.[4][5][6] 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.[7]

Side effects
Common[1][3]
Unknown frequency[1][3]
Rare[1][3]

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.[9] In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor.[10]

Macromolecule (Receptor or transporter protein)Ki [nM][9]
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

Names

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

See also

References
  1. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  2. "Zotepine". Martindale: The Complete Drug Reference. Royal Pharmaceutical Society of Great Britain. 16 August 2013. Retrieved 2 November 2013.
  3. British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
  4. Chan HY, Jou SH, Juang YY, Chang CJ, Chen JJ, Chen CH, Chiu NY (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. 64 (2): 162–9. doi:10.1111/j.1440-1819.2010.02066.x. PMID 20447012. S2CID 27657241.
  5. Harada T, Otsuki S (1986). "Antimanic effect of zotepine". Clinical Therapeutics. 8 (4): 406–14. PMID 3089626.
  6. Amann B, Sterr A, Mergl R, Dittmann S, Seemüller F, Dobmeier M, et al. (October 2005). "Zotepine loading in acute and severely manic patients: a pilot study". Bipolar Disorders. 7 (5): 471–6. doi:10.1111/j.1399-5618.2005.00241.x. PMID 16176441.
  7. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
  8. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
  9. National Institute of Mental Health (12 January 2011). "PDSD Ki Database". Chapel Hill (NC): University of North Carolina. Archived from the original on November 8, 2013. Retrieved 2 November 2013.
  10. Shobo M, Kondo Y, Yamada H, Mihara T, Yamamoto N, Katsuoka M, et al. (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. 333 (3): 772–81. doi:10.1124/jpet.110.166264. PMID 20223878. S2CID 185592.

Further reading
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