Product Code Database
Flupentixol (INN), also known as flupenthixol (former BAN), marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a Combination drug containing both melitracen (a tricyclic antidepressant) and flupentixol (marketed as Deanxit).
Flupentixol is not approved for use in the United States. It is, however, approved for use in the United Kingdom, Australia, (2025). 9780980579093, The Australian Medicines Handbook Unit Trust. ISBN 9780980579093 Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.
Flupentixol is also used in low doses as an antidepressant. There is tentative evidence that it reduces the rate of deliberate self-harm, among those who self-harm repeatedly.
Acronyms used:
A study measuring the in vivo receptor occupancies of 13 schizophrenic patients treated with 5.7 ± 1.4 mg/day of flupentixol found 50-70% receptor occupancy for D2, 20 ± 5% for D1, and 20 ± 10% for 5-HT2A.
Its antipsychotic effects are predominantly a function of D2 antagonism.
Its antidepressant effects at lower doses are not well understood; however, it may be mediated by functional selectivity and/or preferentially binding to D2 at low doses, resulting in increased postsynaptic activation via higher dopamine levels. Flupentixol's demonstrated ability to raise dopamine levels in mice and flies lends credibility to the supposition of autoreceptor bias. Functional selectivity may be responsible through causing preferential autoreceptor binding or other means. The effective dosage guideline for an antipsychotic is very closely related to its receptor residency time (i.e., where drugs like aripiprazole take several minutes or more to disassociate from a receptor while drugs like quetiapine and clozapine—with guideline dosages in the hundreds of milligrams—take under 30s) and long receptor residency time is strongly correlated with likehood of pronounced functional selectivity; thus, with a maximum guideline dose of only 18 mg/day for schizophrenia, there is a significant possibility of this drug possessing unique signalling characteristics that permit counterintuitive dopaminergic action at low doses.
Flupentixol also inhibits tubulin polymerization.
Adverse effects
Adverse effect incidence
Interactions
It should not be used concomitantly with medications known to prolong the QTc interval (e.g., 5-HT3 antagonists, tricyclic antidepressants, citalopram, etc.) as this may lead to an increased risk of QTc interval prolongation. Neither should it be given concurrently with lithium (medication) as it may increase the risk of lithium toxicity and neuroleptic malignant syndrome. It should not be given concurrently with other antipsychotics due to the potential for this to increase the risk of side effects, especially neurological side effects such as neuroleptic malignant syndrome. It should be avoided in patients on CNS depressants such as opioids, alcohol and barbiturates.
Contraindications
It should not be given in the following disease states:
Pharmacology
Pharmacodynamics
Binding profile
— — — Neg. 474 (MB) 120 162.5 >1000 5.73
HFC – Human frontal cortex receptor
MB – Mouse brain receptor
RC – Cloned rat receptor
Pharmacokinetics
History
In March 1963 the Danish pharmaceutical company Lundbeck began research into further agents for schizophrenia, having already developed the thioxanthene derivatives clopenthixol and chlorprothixene. By 1965 the promising agent flupenthixol had been developed and trialled in two hospitals in Vienna by Austrian psychiatrist Heinrich Gross. The long- acting decanoate preparation was synthesised in 1967 and introduced into hospital practice in Sweden in 1968, with a reduction in relapses among patients who were put on the depot.
|
|
