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| Trade names | Clopixol |
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| Routes of administration | Oral,IM |
| Drug class | Typical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | 49% (oral) |
| Protein binding | 98% |
| Metabolism | Liver (CYP2D6 andCYP3A4-mediated) |
| Eliminationhalf-life | 20 hours (oral), 19 days (IM) |
| Excretion | Feces |
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| ECHA InfoCard | 100.053.398 |
| Chemical and physical data | |
| Formula | C22H25ClN2OS |
| Molar mass | 400.97 g·mol−1 |
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Zuclopenthixol (brand namesCisordinol,Clopixol and others), also known aszuclopentixol, is a medication used to treatschizophrenia and otherpsychoses. It is classed, pharmacologically, as atypical antipsychotic. Chemically it is athioxanthene. It is thecis-isomer ofclopenthixol (Sordinol, Ciatyl).[3] Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.[citation needed]
Zuclopenthixol is aD1 and D2 antagonist,α1-adrenergic and5-HT2 antagonist.[4] While it is approved for use in Australia, Canada, Ireland, India, New Zealand, Singapore, South Africa and the UK, it is not approved for use in the United States.[5][6]
Zuclopenthixol is available in three majorpreparations:
It is also used in the treatment of acutebipolar mania.
As a long-acting injection, zuclopenthixol decanoate comes in a 200 mg and 500 mg ampoule. Doses can vary from 50 mg weekly to the maximum licensed dose of 600 mg weekly. In general, the lowest effective dose to prevent relapse is preferred. The interval may be shorter as a patient starts on the medication before extending to 3 weekly intervals subsequently. The dose should be reviewed and reduced if side effects occur, though in the short-term an anticholinergic medicationbenztropine may be helpful for tremor and stiffness, whilediazepam may be helpful for akathisia. 100 mg of zuclopenthixol decanoate is roughly equivalent to 20 mg of flupentixol decanoate or 12.5 mg offluphenazine decanoate.
In oral form zuclopenthixol is available in 2, 10, 25 and 40 mg tablets, with a dose range of 20–60 mg daily.[11]
Chronic administration of zuclopenthixol (30 mg/kg/day for two years) in rats resulted in small, but significant, increases in the incidence of thyroid parafollicular carcinomas and, in females, of mammary adenocarcinomas and of pancreatic islet cell adenomas and carcinomas. An increase in the incidence of mammary adenocarcinomas is a common finding for D2 antagonists which increase prolactin secretion when administered to rats. An increase in the incidence of pancreatic islet cell tumours has been observed for some other D2 antagonists. The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear.
Withdrawal syndrome: Abrupt cessation of therapy may cause acute withdrawal symptoms (eg, nausea, vomiting, or insomnia). Symptoms usually begin in 1 to 4 days of withdrawal and subside within 1 to 2 weeks.[12][13]
Other permanent side effects are similar to many other typical antipsychotics, namelyextrapyramidal symptoms as a result of dopamine blockade in subcortical areas of the brain. This may result in symptoms similar to those seen inParkinson's disease and include a restlessness and inability to sit still known asakathisia, a slow tremor and stiffness of the limbs.[10] Zuclopenthixol is thought to be more sedating than the relatedflupentixol, though possibly less likely to induce extrapyramidal symptoms than other typical depots.[7] As with other dopamine antagonists, zuclopenthixol may sometimes elevateprolactin levels; this may occasionally result inamenorrhoea orgalactorrhoea in severe cases.Neuroleptic malignant syndrome is a rare but potentially fatal side effect. Any unexpected deterioration in mental state with confusion and muscle stiffness should be seen by a physician.
Zuclopenthixol decanoate induces a transient dose-dependent sedation. However, if the patient is switched to maintenance treatment with zuclopenthixol decanoate from oral zuclopenthixol or from i.m. zuclopenthixol acetate the sedation will be no problem. Tolerance to the unspecific sedative effect develops rapidly.[14]
Zuclopenthixol antagonises both dopamineD1 andD2 receptors,α1-adrenoceptors and5-HT2 receptors with a high affinity, but has no affinity formuscarinic acetylcholine receptors. It weakly antagonises thehistamine (H1) receptor but has noα2-adrenoceptor blocking activity[citation needed].
Evidence fromin vitro work and clinical sources (i.e. therapeutic drug monitoring databases) suggests that bothCYP2D6 andCYP3A4 play important roles in zuclopenthixol metabolism.[16]
| Medication | Brand name | Class | Vehicle | Dosage | Tmax | t1/2 single | t1/2 multiple | logPc | Ref |
|---|---|---|---|---|---|---|---|---|---|
| Aripiprazole lauroxil | Aristada | Atypical | Watera | 441–1064 mg/4–8 weeks | 24–35 days | ? | 54–57 days | 7.9–10.0 | |
| Aripiprazole monohydrate | Abilify Maintena | Atypical | Watera | 300–400 mg/4 weeks | 7 days | ? | 30–47 days | 4.9–5.2 | |
| Bromperidol decanoate | Impromen Decanoas | Typical | Sesame oil | 40–300 mg/4 weeks | 3–9 days | ? | 21–25 days | 7.9 | [17] |
| Clopentixol decanoate | Sordinol Depot | Typical | Viscoleob | 50–600 mg/1–4 weeks | 4–7 days | ? | 19 days | 9.0 | [18] |
| Flupentixol decanoate | Depixol | Typical | Viscoleob | 10–200 mg/2–4 weeks | 4–10 days | 8 days | 17 days | 7.2–9.2 | [18][19] |
| Fluphenazine decanoate | Prolixin Decanoate | Typical | Sesame oil | 12.5–100 mg/2–5 weeks | 1–2 days | 1–10 days | 14–100 days | 7.2–9.0 | [20][21][22] |
| Fluphenazine enanthate | Prolixin Enanthate | Typical | Sesame oil | 12.5–100 mg/1–4 weeks | 2–3 days | 4 days | ? | 6.4–7.4 | [21] |
| Fluspirilene | Imap, Redeptin | Typical | Watera | 2–12 mg/1 week | 1–8 days | 7 days | ? | 5.2–5.8 | [23] |
| Haloperidol decanoate | Haldol Decanoate | Typical | Sesame oil | 20–400 mg/2–4 weeks | 3–9 days | 18–21 days | 7.2–7.9 | [24][25] | |
| Olanzapine pamoate | Zyprexa Relprevv | Atypical | Watera | 150–405 mg/2–4 weeks | 7 days | ? | 30 days | – | |
| Oxyprothepin decanoate | Meclopin | Typical | ? | ? | ? | ? | ? | 8.5–8.7 | |
| Paliperidone palmitate | Invega Sustenna | Atypical | Watera | 39–819 mg/4–12 weeks | 13–33 days | 25–139 days | ? | 8.1–10.1 | |
| Perphenazine decanoate | Trilafon Dekanoat | Typical | Sesame oil | 50–200 mg/2–4 weeks | ? | ? | 27 days | 8.9 | |
| Perphenazine enanthate | Trilafon Enanthate | Typical | Sesame oil | 25–200 mg/2 weeks | 2–3 days | ? | 4–7 days | 6.4–7.2 | [26] |
| Pipotiazine palmitate | Piportil Longum | Typical | Viscoleob | 25–400 mg/4 weeks | 9–10 days | ? | 14–21 days | 8.5–11.6 | [19] |
| Pipotiazine undecylenate | Piportil Medium | Typical | Sesame oil | 100–200 mg/2 weeks | ? | ? | ? | 8.4 | |
| Risperidone | Risperdal Consta | Atypical | Microspheres | 12.5–75 mg/2 weeks | 21 days | ? | 3–6 days | – | |
| Zuclopentixol acetate | Clopixol Acuphase | Typical | Viscoleob | 50–200 mg/1–3 days | 1–2 days | 1–2 days | 4.7–4.9 | ||
| Zuclopentixol decanoate | Clopixol Depot | Typical | Viscoleob | 50–800 mg/2–4 weeks | 4–9 days | ? | 11–21 days | 7.5–9.0 | |
| Note: All byintramuscular injection.Footnotes:a =Microcrystalline ornanocrystallineaqueous suspension.b = Low-viscosityvegetable oil (specificallyfractionated coconut oil withmedium-chain triglycerides).c = Predicted, fromPubChem andDrugBank.Sources:Main: See template. | |||||||||
Zuclopenthixol was introduced by Lundbeck in 1978.[27]