Inhibition of neurotransmitter receptor binding by ergot derivatives

Bromocriptine, lergotrile, lisuride, metergoline, and the Sandoz ergot derivatives 25-397, 29-712, and 29-717 have been tested for their ability to inhibit the synaptic receptor binding of spiroperidol, 5-hydroxytryptamine (5-HT), d-lysergic acid diethylamide (LSD), quinuclidinyl benzilate (QNB), WB.4101, and gamma-aminobutyric acid (GABA). Only GABA binding was not affected, and QNB binding was decreased only by lergotrile and metergoline at high concentrations. The most potent inhibitors of the other ligands were bromocriptine and lisuride for spiroperidol (1-2 nMM), metergoline for 5-HT (29 nM), lisuride for LSD (15 nM), and lergotrile for WB.4101 (17 nM). The direct receptor effects of the ergot derivatives in vitro may contribute to understanding their in vivo effects on behavior and in predicting their therapeutic potential in neurological and neuroendocrine disorders.