Zuclopenthixol
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Product Description
Zuclopenthixol, also known as Zuclopentixol or Zuclopenthixolum, is a thioxanthene-based antipsychotic agent that acts as a dopamine D₁/D₂ receptor antagonist. It is primarily used to treat schizophrenia and other psychotic disorders, with major brands including Cisordinol, Acuphase, and Clopixol. The drug is available in liquid form and as long-acting injectable esters, such as zuclopenthixol acetate and zuclopenthixol decanoate. It is metabolized by Cytochrome P450 2D6 and is approved for use in Canada, though not in the United States. Studies have shown that zuclopenthixol can facilitate memory retrieval in rats, possibly through noradrenergic and serotonergic mechanisms, making it a potentially better alternative to other antipsychotics that may impair cognitive function. However, it can also cause tardive dyskinesia, a condition that may improve when switching to other long-acting atypical antipsychotics like paliperidone palmitate.
Related Studies
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Randomised Clinical Trial Comparing Oral vs Depot Formulations:
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Purpose: To determine if depot formulations reduce violence in outpatients with schizophrenia compared to oral administration.
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Methods: 46 previously violent patients with schizophrenia were randomized to receive oral or depot zuclopenthixol for 1 year. Treatment adherence and violent behavior were assessed monthly.
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Results: Violence was inversely proportional to treatment adherence. The depot group showed lower frequency of violent acts. Treatment non-adherence was the best predictor of violence.
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Conclusion: Depot formulations may benefit patients with schizophrenia and prior violent behavior by improving treatment compliance.
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Refractory Schizophrenia Treated with Clozapine Combined with Zuclopenthixol:
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Case Report: A patient with refractory schizophrenia showed significant improvement in positive symptoms after adding zuclopenthixol to clozapine treatment.
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Conclusion: Zuclopenthixol can be an effective adjunctive treatment in patients with refractory schizophrenia who do not respond to clozapine alone.
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Voltammetric Investigation of Oxidation of Zuclopenthixol:
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Objective: To study the electrochemical behavior of zuclopenthixol and develop a differential pulse voltammetric method for its analysis in pharmaceutical preparations.
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Results: The method allows for the determination of zuclopenthixol concentrations in the range of 8×10⁻⁷–2×10⁻⁴ M, applicable to tablets, oral drops, and drug dissolution studies.
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Conclusion: Provides a reliable method for the analysis of zuclopenthixol in various formulations.
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Pharmacological Class and Mechanism of Action
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Class: First-generation (typical) antipsychotic of the thioxanthene group.
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Primary Mechanism: Potent dopamine D1 and D2 receptor antagonist in the mesolimbic pathway of the brain, reducing positive symptoms of psychosis such as hallucinations and delusions.
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Additional Effects: Antagonist effects on serotonin (5-HT2), histamine (H1), and alpha-adrenergic receptors, contributing to therapeutic effects and side effect profile.
Clinical Use
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Main Clinical Use: Treatment of schizophrenia and acute psychosis.
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Key Formulations:
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Oral Tablets: For maintenance therapy (e.g., Cisordinol®, Clopixol®).
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Long-Acting Depot Injection: Zuclopenthixol Decanoate, administered by deep intramuscular injection every 2-4 weeks, ensuring stable drug levels and improving patient compliance.
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Short-Acting Acetate Injection: Zuclopenthixol Acetate, used for rapid tranquilization of patients with acute psychosis, effective within a few hours and lasting for 2-3 days (e.g., Clopixol Acuphase®).
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Uses
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Treatment of Schizophrenia and Psychoses: Zuclopenthixol is primarily used for managing schizophrenia and other psychotic disorders.
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Acute and Chronic Management: Available in oral and injectable forms for both acute and long-term treatment.
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Improving Treatment Adherence: Long-acting depot injections help improve adherence in patients with a history of non-compliance.
Basic Identification
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Name: Zuclopenthixol (also known as Zuclopenthixol Hydrochloride in its common salt form)
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CAS Number: 53772-83-1
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Molecular Formula: C₂₂H₂₅ClN₂OS
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Molecular Weight: 400.96 g/mol
Chemical Structure and Properties
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Thioxanthene Core: The "S" and the carbon skeleton form the thioxanthene tricyclic system, which is the core structure of this drug class. It is structurally similar to phenothiazines but with a carbon atom replacing the nitrogen in the central ring and a double bond to the side chain.
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Piperazine Side Chain: The "N₂" indicates a piperazine ring incorporated into the side chain, contributing to its strong dopamine receptor blockade.
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Chlorine Substituent: The "Cl" atom is typically attached to the thioxanthene ring system at position 2, increasing its antipsychotic potency.
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Double Bond Isomerism: Zuclopenthixol has a double bond in its side chain, giving rise to geometric isomers (cis (Z) and trans (E)). The cis (Z)-isomer is the active antipsychotic form, while the trans (E)-isomer is known as Flupentixol.
Common Side Effects
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Extrapyramidal Symptoms (EPS): Dystonia, akathisia, parkinsonism, and tardive dyskinesia (due to D2 blockade in the nigrostriatal pathway).
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Sedation: Due to H1 histamine receptor blockade.
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Anticholinergic Effects: Dry mouth, blurred vision, constipation.
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Orthostatic Hypotension: Due to alpha-adrenergic receptor blockade.
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Hyperprolactinemia: Due to D2 blockade in the tuberoinfundibular pathway.
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Weight Gain.