Thioridazine is a first-generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias and QT interval prolongation. Thioridazine exerts antipsychotic effects primarily via dopamine D2 receptor antagonism in mesolimbic pathways and also displays affinity for 5-HT2, alpha1-adrenergic, histamine H1 and muscarinic receptors, which contributes to sedation, orthostatic hypotension and anticholinergic effects. It is extensively metabolized in the liver by CYP enzymes with N-demethylation and sulfoxidation pathways producing active and inactive metabolites including thioridazine sulfoxide; the parent compound and metabolites are highly protein bound and show variable elimination half life depending on metabolic phenotype. Clinically relevant safety concerns included dose-dependent QT prolongation due to hERG potassium channel inhibition and cumulative retinal and corneal toxicity with prolonged exposure.
Parent: Thioridazine
Parent: Thioridazine
Parent: Thioridazine/ Thioridazine Hydrochloride
Parent: Thioridazine
Parent: Thioridazine
Parent: Thioridazine
Parent: Thioridazine
Typical pharmaceutical active ingredient specifications for thioridazine hydrochloride control assay and related substances according to compendial and ICH guidance. Representative assay acceptance is approximately 98.0 to 102.0 percent of declared potency. Typical limits for related substances used by manufacturers are individual identified impurities not greater than 0.2 to 0.3 percent and unspecified impurities controlled below 0.1 to 0.2 percent depending on qualification status, with total impurities commonly limited to 0.5 to 1.0 percent. Common related compounds and process or degradation impurities include desmethylthioridazine, thioridazine sulfoxide, thioridazine sulfone, thioridazine N-oxide and trace phenothiazine backbone degradation products; typical provisional limits are for desmethylthioridazine up to 0.2 percent, thioridazine sulfoxide up to 0.3 percent and other specified impurities generally below 0.1 to 0.2 percent, subject to manufacturer and regulatory qualification. Genotoxic impurity risk must be assessed and controlled in line with ICH M7 and impurity identification thresholds are determined by daily patient exposure and analytical capability. Routine control is performed by validated HPLC or LC-MS methods and stability studies to monitor formation of degradation products.
Thioridazine was marketed under the brand name Mellaril in many countries. Other regional trade names existed historically, but the original branded product was withdrawn from most markets in 2005.
Thioridazine primarily antagonizes dopamine D2 receptors in the central nervous system, reducing positive psychotic symptoms. It also blocks 5-HT2, alpha1-adrenergic, histamine H1 and muscarinic receptors, contributing to additional clinical effects and adverse events. Cardiac risk is related to inhibition of the cardiac hERG potassium channel leading to QT interval prolongation.
Thioridazine can produce pigmentary retinopathy and corneal deposits after prolonged or high-dose exposure, manifesting as decreased visual acuity, constricted visual fields and color vision changes. Retinal damage may be progressive and in some cases irreversible, so ophthalmological monitoring was recommended historically for long term use.
No, Thorazine is a trade name for chlorpromazine, a different phenothiazine antipsychotic. Chlorpromazine and thioridazine share the phenothiazine class but differ in receptor binding profiles, clinical properties and safety risks.
