Chemical formula: C₂₃H₂₅F₃N₂OS Molecular mass: 434.52 g/mol PubChem compound: 5281881
Flupentixol is a neuroleptic of the thioxanthene series.
The antipsychotic effect of antipsychotics is related to their dopamine receptor blocking effect. 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 that for D2 receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity for D2 receptors.
In the traditional tests for antipsychotic effect, eg antagonism of stereotypic behaviour induced by dopamine agonists, the chemical groups of antipsychotics mentioned reveal equal but dosage-dependent activity. However, the antistereotypic effects of phenothiazines, butyrophenones, diphenylbutylpiperidines, and benzamides is strongly counteracted by the anticholinergic drug scopolamine, while the antistereotypic effect of thioxanthenes, eg flupentixol is not, or only very slightly, influenced by concomitant treatment with anticholinergics.
Oral administration to volunteers (8 mg single dose and 1.5 mg/day) and patients (5-60 mg/day) resulted in serum drug concentration curves with a maximum around four hours after administration. Mean biological half-life was about 35 hours in patients. No difference was seen in patients between half-lives estimated after single-dose administration and those estimated after repeated administration. Mean oral bioavailability of flupentixol varied between 40% and 55%.
By esterification of flupentixol with decanoic acid flupentixol has been converted to a highly lipophilic substance, flupentixol decanoate. When dissolved in oil and injected intramuscularly this substance diffuses slowly into the surrounding body water, where enzymatic breakdown occurs releasing the active component flupentixol. The duration of action is 2-4 weeks with maximum serum levels being reached by the end of the first week after injection.
Flupentixol is distributed in the body in a similar way to other antipsychotics; with the highest concentrations of drug and metabolites in liver lungs, intestines and kidneys and lower concentrations in heart, spleen, brain and blood. The apparent volume of distribution is about 14 L/kg and the protein binding >95%.
Flupentixol crosses the placental barrier in small amounts; it is also excreted in breast milk in very small amounts.
The metabolism of flupentixol proceeds via three main routes -sulphoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are devoid of psychopharmacological activity. The excretion proceeds mainly with the faeces but also to some degree with the urine. System; clearance is about 0.4-0.5 L/min.
In fertility studies in rats, flupentixol slightly affected the pregnancy rate of female rats. Animal reproduction studies in mice, rats and rabbits have not shown evidence of teratogenic effects. Embryotoxic effects in terms of increased post implantation loss/increased absorption rates or occasional abortions were seen in rats and rabbits at doses associated with maternal toxicity.
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