Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice

Reproductive toxicology studies supporting the safety of molindone, a dopamine receptor antagonist

“…The effects on estrous cyclicity were expected based on the primary mechanism of action of molindone HCl as an antagonist of the dopamine D 2 receptor and the expected increase in prolactin secretion with dopamine antagonism (Rehm, Stanislaus, & Wier, ; Smith et al, ). Indeed, molindone HCl administration causes dose‐dependent increases in prolactin in rats (Krishna et al, ) and mice (Krishna et al, ), suggesting that estrous cycle changes in the current fertility study are pharmacology related.…”

“…Molindone is a dopamine receptor antagonist, which has the potential for causing increases in prolactin levels. Prolactin secretion is negatively modulated by dopamine release (Ben‐Jonathan, Lapensee, & Lapensee, ), and administration of neuroleptic agents is associated with increased prolactin secretion in rodents (Krishna et al, ; Krishna, Ganiger, Kannan, Gopalakrishnan, & Goel, ) and humans, as well as downstream manifestations of hyperprolactinemia (Peuskens, Pani, Detraux, & De Hert, ). Although prolactin is regulated by dopamine in animals and humans, the role of prolactin in reproductive function varies across species.…”