Flupentixol

The mechanism of action of flupentixol is not completely understood. The antipsychotic actions are mainly thought to arise from cis(Z)-flupentixol, the active stereoisomer, acting as an antagonist at both dopamine D1 and D2 receptors with equal affinities. Schizophrenia is a mental illness characterized by positive (such as hallucinations and delusions) and negative (such as affect flattening and apathy) symptoms. While several neurotransmitter systems are implicated in the pathophysiologic processes leading to the development of symptoms, the dopamine and glutamate systems have been extensively studied. It is generally understood that positive symptoms of schizophrenia arise from a dysregulated striatal dopamine pathway, leading to hyperstimulation of D2 receptors. Many antipsychotic agents work by blocking D2 receptors as antagonists; similarly, cis(Z)-flupentixol, the active stereoisomer, is an antagonist at D2 receptors. However, there is now evidence that antipsychotic agents can work by blocking other dopamine receptor subtypes, such as D1, D3, or D4 receptors. One study showed that cis(Z)-flupentixol is an antagonist at both dopamine D1 and D2 receptors with equal affinities, and binds to D3 and D4 receptors with lower affinities. It also binds to alpha-1 adrenoceptors. Antidepressant effects of flupentixol are understood to be mediated by antagonism at 5-HT2A receptors, which are commonly downregulated following repeated antidepressant treatment. Flupentixol also binds to 5-HT2C receptors.