Zotepine

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Zotepine
Zotepine2D1.svg
Zotepine3Dan3.gif
Systematic (IUPAC) name
2-[(8-​chlorodibenzo(b,f)​thiepin-​10-​yl)oxy]-​N,N-​dimethylethanamine
Clinical data
Trade names Zoleptil
AHFS/Drugs.com International Drug Names
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 7-13% (Oral)[1]
Metabolism N-desmethylation to norzotepine (30-40%)[1]
Half-life 13.7-15.9 hours, 12 hours (Norzotepine)[1]
Excretion 17% (Urine)[1]
Identifiers
CAS number 26615-21-4 N
ATC code N05AX11
PubChem CID 5736
IUPHAR ligand 103
DrugBank none
ChemSpider 5534 YesY
UNII U29O83JAZW YesY
KEGG D01321 YesY
ChEBI CHEBI:32316 YesY
ChEMBL CHEMBL285802 YesY
Chemical data
Formula C18H18ClNOS 
Mol. mass 331.86
 N (what is this?)  (verify)

Zotepine (brand names: Losizopilon (JP), Lodopin (ID, JP), Setous (JP), Zoleptil (CZ, PT, TR, UK†); where † indicates a formulation that has been discontinued) 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[edit]

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]

Side effects[edit]

Common[1][3]
Unknown Frequency[1][3]
Rare[1][3]

Pharmacology[edit]

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

Macromolecule (Receptor or transporter protein) Ki [nM][8]
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

Dosing[edit]

The most common dosage used is 150 mg daily. It is suggested that zotepine therapy starts at 75 mg to 150 mg divided into three daily doses. Some people may need to have their dosage increased to 300 mg.[2]

50 mg Lodopin® pills

References[edit]

  1. ^ a b c d e f g Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  2. ^ a b c "Zotepine". Martindale: The Complete Drug Reference. Royal Pharmaceutical Society of Great Britain. 16 August 2013. Retrieved 2 November 2013. 
  3. ^ a b c d 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): 162–169. doi:10.1111/j.1440-1819.2010.02066.x. PMID 20447012. 
  5. ^ Harada, T; Otsuki, S (1986). "Antimanic effect of zotepine". Clinical Therapeutics 8 (4): 406–414. PMID 3089626. 
  6. ^ Amann, B; Sterr, A; Mergl, R; Dittmann, S; Seemüller, F; Dobmeier, M; Orth, M; Schaefer, M; Grunze, H (October 2005). "Zotepine loading in acute and severely manic patients: a pilot study". Bipolar Disorders 7 (5): 471–476. doi:10.1111/j.1399-5618.2005.00241.x. PMID 16176441. 
  7. ^ a b c Leucht, S; Cipriani, A; Spineli, L; Mavridis, D; Orey, D; Richter, F; Samara, M; Barbui, C; Engel, RR; Geddes, JR; Kissling, W; Stapf, MP; Lässig, B; Salanti, G; Davis, JM (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. 
  8. ^ a b National Institute of Mental Health (12 January 2011). "PDSD Ki Database". Chapel Hill (NC): University of North Carolina. Retrieved 2 November 2013. 
  9. ^ Shobo, M; Kondo, Y; Yamada, H; Mihara, T; Yamamoto, N; Katsuoka, M; Harada, K; Ni, K; Matsuoka, N (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): 772–781. doi:10.1124/jpet.110.166264. PMID 20223878.