Chemistry:Zotepine

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Short description: Atypical antipsychotic medication
Zotepine
Zotepine.svg
Zotepine-optimized-ball-and-stick.png
Clinical data
Trade namesZoleptil
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)
  • 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
Chemical and physical data
FormulaC18H18ClNOS
Molar mass331.86 g·mol−1
3D model (JSmol)
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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.[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]
SERT 151
NET 530
DAT 3621
5-HT1A 470.5
5-HT1B 59.5
5-HT1D 119
5-HT1E 700
5-HT2A 2.7
5-HT2C 2.6
5-HT3 472
5-HT5A 29
5-HT6 6
5-HT7 12
α1A 7
α1B 5
α2A 180
α2B 5.35
α2C 106
M1 18
M2 140
M3 73
M4 77
M5 260
D1 71
D2 25
D2S 5.4
D2L 11
D3 6.4
D4 18
D5 248
H1 3.21
H2 500
H4 1977

Society and culture

Brand names

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

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  2. ↑ 2.0 2.1 "Zotepine". Martindale: The Complete Drug Reference. Royal Pharmaceutical Society of Great Britain. 16 August 2013. http://www.medicinescomplete.com/mc/martindale/current/2479-d.htm?. 
  3. ↑ 3.0 3.1 3.2 3.3 British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
  4. ↑ "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. April 2010. doi:10.1111/j.1440-1819.2010.02066.x. PMID 20447012. 
  5. ↑ "Antimanic effect of zotepine". Clinical Therapeutics 8 (4): 406–14. 1986. PMID 3089626. 
  6. ↑ "Zotepine loading in acute and severely manic patients: a pilot study". Bipolar Disorders 7 (5): 471–6. October 2005. doi:10.1111/j.1399-5618.2005.00241.x. PMID 16176441. 
  7. ↑ "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet 382 (9896): 951–62. September 2013. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. 
  8. ↑ 8.0 8.1 8.2 "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet 382 (9896): 951–62. September 2013. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. 
  9. ↑ 9.0 9.1 National Institute of Mental Health (12 January 2011). "PDSD Ki Database". University of North Carolina. http://pdsp.med.unc.edu/pdsp.php. 
  10. ↑ "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. June 2010. doi:10.1124/jpet.110.166264. PMID 20223878. 

Further reading



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