indication

Molindone is used for the management of the manifestations of psychotic disorders.

pharmacology

Molindone is a dihydroindolone compound which is not structurally related to the phenothiazines, the butyrophenones, or the thioxanthenes. Molindone has a pharmacological profile in laboratory animals which predominantly resembles that of major tranquilizers causing reduction of spontaneous locomotion and aggressiveness, suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity induced by amphetamines. In addition, molindone antagonizes the depression caused by the tranquilizing agent tetrabenazine.

mechanism of action

The exact mechanism has not been established, however, based on electroencephalogram (EEG) studies, molindone is thought to act by occupying (antagonizing) dopamine (D2) receptor sites in the reticular limbic systems in the brain, thus decreasing dopamine activity. Decreased dopamine activity results in decreased physiological effects normally induced by excessive dopamine stimulation, such as those typically seen in manifestations of psychotic disorders.

biotransformation

Most likely hepatic. 36 metabolites have been recognized, some of which may be active.

absorption

Rapidly absorbed from the gastrointestinal tract following oral administration.

route of elimination

Human metabolic studies show molindone to be rapidly absorbed and metabolized when given orally. There are 36 recognized metabolites with less than 2-3% unmetabolized molindone being excreted in urine and feces.

drug interactions

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Molindone, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Trimethobenzamide: Trimethobenzamide and Molindone, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Molindone, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Molindone, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.