Marketed as Clopixol in Australia, Zuclopenthixol Dihidrochloride is part of the drug class Antipsychotics. It is comonly used to treat acute and chronic schizophrenia, other psychoses and the manic phase of manic depression. It's function is basically the opposite of Dexamphetamine. Like Dexamphetamine, it targets the patient's Central nervous system and is most commonly administered in tablet form.

The following clinical information is taken from an Australian drug database for Clinicians.


Clopixol Acuphase: zuclopenthixol acetate. Clopixol Depot: zuclopenthixol decanoate. Clopixol tablets: zuclopenthixol dihydrochloride.

Clopixol Accuphase, Clopixol Depot: fractionated coconut oil. Clopixol tablets: potato starch, lactose, microcrystalline cellulose, povidone/ vinylacetate copolymer, glycerol, talc, hydogenated castor oil and magnesium stearate, with a coating of hypromellose and macrogol coloured with titanium dioxide and ferric oxide.


Mechanism of action

The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking activity. The thioxanthenes have high affinity for both the adenylate cyclase coupled dopamine D1-receptors and for the dopamine D2-receptors; in the phenothiazine group the affinity for D1-receptors is much lower than for D2-receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity for D2-receptors.

In the traditional tests for antipsychotic effect, e.g. antagonism of stereotypic behaviour induced by dopamine agonists, the mentioned chemical groups of neuroleptics exhibit equal but dose dependent activity. However the antistereotypic effect of butyrophenones, diphenylbutylpiperidines and benzamides is strongly counteracted by the anticholinergic drug scopolamine, that of the phenothiazines less so, while the antistereotypic effect of the thioxanthenes, e.g. zuclopenthixol, is not influenced (or is only very slightly influenced) by concomitant treatment with anticholinergics. Like most other neuroleptics, zuclopenthixol increases the serum prolactin level.

A clear relationship between serum levels and clinical effects of zuclopenthixol has not been established. However data from open trials of zuclopenthixol in the treatment of mania and acute paranoid psychosis indicate that the minimum effective serum levels are 5 nanogram/mL (12.5 nanomol/L) in patients with acute mania of moderate severity, 3 to 4 nanogram/mL (7.5 to 10 nanomol/L) in moderately psychotic patients (brief psychiatric rating scale (BPRS) 26 to 30 points), and 6 to 8 nanogram/L (15 to 20 nanomol/L) in severely psychotic patients (BPRS 31 to 38 points). Clopixol tablets when given within the dosage recommendation provide adequate zuclopenthixol serum levels for effective control of psychoses.

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.


As for other neuroleptics, zuclopenthixol is distributed with highest concentrations of drug and metabolites in the liver, lungs, intestines and kidneys and lower concentrations in the heart, spleen, brain and blood. The apparent volume of distribution is 20 L/kg and protein binding approximately 98% at concentrations above the therapeutic range.
The metabolism of zuclopenthixol is mainly by means of sulfoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are devoid of psychopharmacological activity. Excretion is mainly via the faecal route and to a smaller degree (about 10%) via the urine. Only about 0.1% of the dose is excreted unchanged in the urine, so the drug load on the kidneys is negligible. The systemic clearance is approximately 0.9 L/minute.
The kinetics appear to be linear, since highly significant correlations exist between dose and serum level, and between dose and area under the serum concentration curve, respectively.


Initiation of therapy

Severe adverse reactions requiring immediate medical attention may occur and are difficult to predict. Therefore, the evaluation of tolerance and response and establishment of adequate maintenance therapy require careful stabilisation of each patient under continuous close medical observation and supervision.

Sedative effects

Since sedation may occur, ambulatory patients receiving Clopixol should be cautioned against activities such as driving a car or operating machinery. Clopixol may enhance the sedative effects of alcohol and other CNS depressant drugs. Dyskinesia. The possibility of the development of irreversible dyskinesia should be borne in mind when patients are on prolonged therapy with Clopixol.

Antiemetic effect

The antiemetic effect observed with zuclopenthixol in animal studies may also occur in humans. Therefore the drug may mask signs of toxicity due to overdosage of other drugs, or it may mask symptoms of diseases such as brain tumour or intestinal obstruction.

Photosensitivity reactions

Photosensitivity reactions, pigmentary retinopathy and lenticular and corneal deposits have been reported with related drugs. Lens opacity has been reported rarely with zuclopenthixol.

Anaphylactoid reactions

The possibility of anaphylactoid reactions occurring in some patients should be borne in mind. Neuroleptic malignant syndrome. A potentially fatal syndrome called neuroleptic malignant syndrome has been reported on occasion with antipsychotic drugs. The syndrome is characterised by muscular rigidity, fever, hyperthermia, altered consciousness and autonomic instability (e.g. tachycardia, labile blood pressure, profuse sweating, dyspnoea). The management of neuroleptic malignant syndrome should include immediate discontinuation of antipsychotic drugs, intensive monitoring of symptoms and treatment of any associated medical problems.



Overdosage is characterised by somnolence, coma, extrapyramidal symptoms, convulsions, cramps, decreased blood pressure, shock and hampered regulation of temperature (hyperthermia or hypothermia).


There is no specific antidote for zuclopenthixol. Treatment should be symptomatic and supportive. Gastric lavage should be carried out immediately after oral ingestion and activated charcoal may be administered. Measures aimed at supporting the respiratory and cardiovascular systems should be instituted. A patent airway should be maintained. If severe hypotension occurs, an intravenous vasopressor drug should be administered immediately. Adrenaline and noradrenaline should not be used, as a further lowering of blood pressure may result. Antiparkinsonian medication should be administered only if extrapyramidal symptoms develop. Zuclopenthixol should be withdrawn until the patient shows signs of relapse and should then be reintroduced at a lower dose.

Source: Source: MIMS Pharmeceutical Database 01/02/2003