Description
Zuclopenthixol is a dopamine receptor antagonist (K
is = 9.8 and 1.5 nM for D
1 and D
2 receptors, respectively). It also binds to serotonin (5-HT) receptor subtypes 5-HT
2 and 5-HT
6, α
1-adrenergic, and histamine receptors (K
is = 7.6, 3, 33, and 169 nM, respectively) but not α
2-adrenergic receptors (K
i = >4,300 nM). Zuclopenthixol inhibits dopamine-induced accumulation of cAMP in rat striatal homogenates (IC
50 = 330 nM; K
i = 16 nM). It decreases stereotypic behavior induced by methylphenidate in mice (ED
50 = 0.8 μmol/kg) and by apomorphine in rats and dogs (ED
50s = 6.0 and 1.3 μmol/kg, respectively). Zuclopenthixol (0.7 and 1.4 mg/kg, i.p.) administered prior to testing enhances memory retrieval in rats in an inhibitory avoidance task without affecting locomotor activity.
Description
Zuclopenthixol is a kind of antipsychotic agent. It is a thioxanthene-based neuroleptic with in vivo action similar to the phenothiazine antipsychotics through antagonizing D1 and D2 dopamine receptors. It has three major formulations form including zuclopenthixol decanoate, zuclopenthixol acetate, and zuclopenthixol dihydrochloride. It can be used for the treatment of schizophrenia and bipolar mania. Besides antagonizing the D1 and D2 dopamine receptors, Zuclopenthixol can also take effect through antagonizing alpha1-adrenergic and 5-HT2 receptors. It can also weakly block the histamine H1 receptor.
Chemical Properties
Pale Yellow Low Melting Solid
Uses
Zuclopenthixol is an anti-psychotic drug. It is an inhibitor of coxsackievirus B3. Also, it is an intermediate used in the synthesis of Zuclopenthixol Decanoate (Z701490), which is used in the maintenance treatment of chronic schizophrenic patients. It is one of the three distinct formulations of Zuclopenthixol namely, zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate.
Uses
The labelled cis(Z)-form of Clopenthixol. Thioxanthene neuroleptic. Antipsychotic.
Uses
The cis(Z)-form of Clopenthixol. Thioxanthene neuroleptic. Antipsychotic.
Definition
ChEBI: The (Z)-isomer of clopenthixol.
Clinical Use
Antipsychotic for schizophrenia and other psychoses
Drug interactions
Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effects.
Analgesics: increased risk of convulsions with
tramadol; enhanced hypotensive and sedative
effects with opioids; increased risk of ventricular
arrhythmias with methadone.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with anti-arrhythmics that prolong
the QT interval - avoid with amiodarone and
disopyramide.
Antibacterials: increased risk of ventricular
arrhythmias with moxifloxacin and parenteral
erythromycin - avoid
Antidepressants: increased level of tricyclics; possible
increased risk of convulsions with vortioxetine.
Antiepileptics: anticonvulsant effect antagonised.
Antimalarials: avoid concomitant use with
artemether/lumefantrine.
Antipsychotics: avoid concomitant use of clozapine
with depot preparations in case of neutropenia;
possible increased risk of ventricular arrhythmias
with risperidone.
Antivirals: concentration possibly increased with
ritonavir.
Atomoxetine: increased risk of ventricular
arrhythmias.
Anxiolytics and hypnotics: increased sedative effects.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol - avoid.
Cytotoxics: increased risk of ventricular arrhythmias
with vandetanib - avoid; increased risk of ventricular
arrhythmias with arsenic trioxide.
Metabolism
Metabolism of zuclopenthixol is by sulphoxidation, sidechain N-dealkylation and glucuronic acid conjugation.
The sulphoxide metabolites are mainly excreted in the
urine while unchanged drug and the dealkylated form
tend to be excreted in the faeces.
References
https://www.drugbank.ca/drugs/DB01624
https://en.wikipedia.org/wiki/Tiabendazole
