Zotepine
 | |
| Clinical data | |
|---|---|
| Trade names | Zoleptil |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| ATC code | N05AX11 (WHO) |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | 7-13% (Oral)[1] |
| Metabolism | N-desmethylation to norzotepine (30-40%)[1] |
| Biological half-life | 13.7-15.9 hours, 12 hours (Norzotepine)[1] |
| Excretion | 17% (Urine)[1] |
| Identifiers | |
| |
| CAS Number |
26615-21-4  |
| PubChem (CID) | 5736 |
| IUPHAR/BPS | 103 |
| DrugBank |
DB09225 |
| ChemSpider |
5534  |
| UNII |
U29O83JAZW |
| KEGG |
D01321 |
| ChEBI |
CHEBI:32316 |
| ChEMBL |
CHEMBL285802 |
| ECHA InfoCard | 100.189.143 |
| Chemical and physical data | |
| Formula | C18H18ClNOS |
| Molar mass | 331.86 |
| 3D model (Jmol) | Interactive image |
| |
| |
| (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
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
- Tachycardia
- Hypotension
- Orthostatic hypotension
- Palpitations
- Hyperprolactinaemia
- Weight gain (produces a similar degree of weight gain to that seen with clozapine and olanzapine treatment)[7]
- Somnolence (2nd highest effect size for causing sedation out of fifteen antipsychotics compared in a recent meta-analysis)[7]
- Extrapyramidal side effects [EPSE] (2nd largest odds ratio for causing EPSE out of fifteen antipsychotics compared in a recent meta-analysis, second only to haloperidol)[7]
- Constipation
- Xerostomia (dry mouth)
- Blurred vision
- Hypersalivation (drooling)
- Mydriasis
- Anxiety
- Agitation
- Rhinitis
- Sexual dysfunction
- Dyspnoea
- Diarrhoea
- Influenza-like symptoms
- Cough
- Vertigo
- Confusion
- Dyspepsia
- Flushing dry skin
- Arthralgia
- Myalgia
- Acne
- Conjunctivitis
- Thrombocythaemia
- QT interval prolongation
- Hyperthermia
- Hypothermia
- Increased serum creatinine
- Hyperglycaemia
- Hypoglycaemia
- Hyperlipidaemia
- Thirst
- Urinary incontinence
- Angle-closure glaucoma
- Agranulocytosis
- Neutropaenia
- Eosinophilia
- Leukocytopenia
- Hypoesthesia
- Anaemia
- Myoclonus
- Myasthenia
- Alopecia
- Thrombocytopaenia
- Bradycardia
- Epistaxis
- Abdominal enlargement
- Deep vein thrombosis
- Paralytic ileus
- Leukopenia
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- Laryngeal edema
- Urinary retention
- Depression
- Ataxia
- Amnesia
- Seizure (dose-dependent risk)[2]
- Metabolic syndrome
- Diabetes mellitus type II
- Cholestasis
- Increased liver enzymes
- Photosensitivity
- Exanthema
- Pruritus
- Hypouricemia
- Oedema
Pharmacology
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
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
See also
- Dosulepin
- Noxiptyline
- Carbinoxamine Diphenhydramine Doxylamine Orphenadrine the termination chain is the same
- Toll-like receptor 4 investigating probable antagonistic (antiinflammatory) property of several TCA based molecules
References
- 1 2 3 4 5 6 7 Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
- 1 2 3 "Zotepine". Martindale: The Complete Drug Reference. Royal Pharmaceutical Society of Great Britain. 16 August 2013. Retrieved 2 November 2013.
- 1 2 3 4 British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
- ↑ 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.
- ↑ Harada, T; Otsuki, S (1986). "Antimanic effect of zotepine". Clinical Therapeutics. 8 (4): 406–414. PMID 3089626.
- ↑ 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.
- 1 2 3 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.
- 1 2 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.
- ↑ 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" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 333 (3): 772–781. doi:10.1124/jpet.110.166264. PMID 20223878.
- http://www.priory.com/focus11.htm
- http://web.archive.org/web/20040619085151/http://www.nyrdtc.nhs.uk:80/docs/nde/Zotepine.pdf -
- LOSIZOPILON SUGAR-COATED TABLETS & FINE GRANULES (PDF)
- ロドピン（ゾテピン） 1982年 精神神経学雑誌
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