Thioridazine is a trifluoro-methyl phenothiazine derivative. Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis. Similar to other first-generation or typical antipsychotics, thioridazine is a medication used to treat schizophrenia. Other indications for use include other psychotic disorders, depressive disorders, pediatric behavioral disorders, and geriatric psychoneurotic manifestations. Positive symptoms are believed to manifest as a result of increased levels of dopamine in the mesolimbic pathway. More specifically, thioridazine blocks DA-2 receptors in the mesolimbic pathway, diminishing positive symptoms. Thioridazine is classified as a low potency first-generation antipsychotic, and as such, is relatively sedating. Thioridazine is a substrate of the hepatic enzyme CYP450 2D6 and is also an inhibitor of the same enzyme. The drug also exhibits activity at muscarinic receptors (most notably the M1 receptor), which is most likely the source of its anticholinergic effects (e.g., dry mouth, constipation, etc.), the alpha 1A adrenergic receptor (which may explain its association with orthostatic hypotension), the H1 histamine receptor (probably accounting for much of its sedating effect), and the hERG gene, which is likely responsible for its cardiotoxicity

Thioridazine Serotonin Antagonist Pathway References