Binding interactions of ergot alkaloids with monoaminergic receptors in the brain.

The interactions of ergot alkaloids and of other drugs with dopamine (DA) and alpha-adrenergic receptors were investigated. The tested ergot alkaloids inhibit synaptosomal tyrosine hydroxylase activity and reverse the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. Thus, ergot alkaloids interact as both agonists and antagonists with the presynaptic DA receptors. Ergot alkaloids also compete effectively for the binding of 3H-DA and 3H-haloperidol to bovine striatal membranes. These results show that these drugs are mixed agonist-antagonists with respect to the postsynaptic DA receptors. To determine the effects of ergot alkaloids and of neuroleptics on the alpha-adrenergic receptors in the CNS, we have measured their effects on the binding of 3H-dihydroergocryptine and 3H-WB-4101 to cerebral cortical membranes. The displacing potencies of the tested ergot alkaloids and of the neuroleptics indicated that they have a high affinity for the alpha-adrenoreceptors in the CNS. The mechanisms underlying the therapeutic efficacy of mixed agonist-antigonists of DA and alpha-adrenergic receptors in Parkinson's disease and in geriatric disorders were considered.