What is the action of molindone?
Molindone is a short-acting antipsychotic.
Molindone, along with other antipsychotic drugs which elicit little or no Parkinsonism, bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.
Molindone is D2-selective in vitro and has a dual D1-D2 receptor profile in vivo.
Molindone can selectively block the presynaptic DA receptors.
Molindone causes a statistically significant up-regulation of both the long and short isoforms of the D2 receptor mRNAs in the prefrontal and temporal cortex, but has no effect on D4 mRNA levels in either cortical or striatal tissue.
Molindone elevates Fos-like immunoreactivity (FLI) in the dorsolateral striatum.
Molindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase.
Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine.