The interactions of bromocriptine and lergotrile with dopamine and α-adrenergic receptors

Abstract

Bromocriptine and lergotrile, which are clinically used as antiparkinsonian (AP) agents, compete for the binding of H³-dopamine, H³-apomorphine, and H³-haloperidol to striatal membrane sites. Lergotrile has a higher affinity for the H³-dopamine binding to bovine striatal membranes than bromocriptine. Lergotrile and bromocriptine are almost equipotent in competing for the binding of H³-apomorphine to rat striatal membranes, but bromocriptine is more potent in competing for the binding of H³-haloperidol than lergotrile. These results indicate that lergotrile and bromocriptine are mixed putative agonist-antagonist with respect to the postsynaptic dopamine receptors. Lergotrile and bromcriptine at higher concentrations inhibit synaptosomal tyrosine hydroxylase activity, and reverse the apomorphine elicited enzyme inhibition. Thus, these ergot alkaloids behave as mixed agonist-antagonist also with respect to the presynaptic dopamine receptors. Bromocriptine and lergotrile, as well as other tested DH-ergot alkaloids and neuroleptics, compete for the binding of theα-antagonist H³-WB-4101 to rat cerebral cortical membranes. The displacing potencies of the tested DH-ergot alkaloids and of the neuroleptics indicate that they have a high affinity for theα-adrenoreceptors in the CNS.