Molindone is a dopamine receptor antagonist.1 It selectively inhibits radioligand binding to dopamine D2 receptors in rat brain homogenates (IC50s = 56 and >10,000 nM for D2 and D1 receptors, respectively), however, it inhibits radioligand binding to both D2 and D1 receptors in vivo (ED50s = 4.9 and 51 mg/kg, respectively). Molindone (0.4-0.8 mg/kg) reverses depression of dopamine neurons induced by D-amphetamine and apomorphine and increases dopamine synthesis and dihydroxyphenylacetic acid levels in the striatum and olfactory tubercles in rats.2 It suppresses spontaneous locomotion and blocks conditioned avoidance responses in male mice and female rats.3 It inhibits climbing behavior in mice induced by the D2 receptor agonist bromocriptine .4 Molindone (0.3-5.6 mg/kg) increases error rates and reduces response rate in pigeons following learned acquisition.5 Formulations containing molindone have been used in the treatment of schizophrenia.
1.Andersen, P.H.Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding to dopamine receptors in vivo in mouse brainEur. J. Pharmacol.146(1)113-120(1988) 2.Bunney, B.S., Roth, R.H., and Aghajanian, G.K.Effects of molindone on central dopaminergic neuronal activity and metabolism: Similarity to other neurolepticsPsychopharmacol. Commun.1(4)349-358(1975) 3.Rubin, A.A., Yen, H.C., and Pfeffer, M.Psychopharmacological profile of molindoneNature216(5115)578-579(1967) 4.Balsara, J.J., Nandal, N.V., Gada, V.P., et al.Antagonism of bromocriptine-induced cage climbing behaviour in mice by the selective D-2 dopamine receptor antagonists, metoclopramide and molindoneIndian J. Physiol. Pharmacol.30(1)85-90(1986) 5.Poling, A., Cleary, J., Berens, K., et al.Neuroleptics and learning: Effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedureJ. Pharmacol. Exp. Ther.255(3)1240-1245(1990)