The selectivity of some ergot derivatives for alpha 1 and alpha 2-adrenoceptors of rat cerebral cortex.
The affinities of several ergot derivatives for rat cerebral cortex alpha 1- and alpha 2-adrenoceptors were assessed using radioligand binding techniques. In most cases both [3H]prazosin (labelling alpha 1-adrenoceptors) and [3H]rauwolscine (labelling alpha 2-adrenoceptors) binding were displaced by the ergot derivatives tested, but with markedly different potency. Generally compounds displayed selectivity toward the alpha 2-adrenoceptor, particularly CQ 32-084, which had a Ki value against [3H]rauwolscine binding of 35 nM, but had little effect on [3H]prazosin binding at concentrations in excess of 5 microM. Lisuride was the most potent displacer of [3H]rauwolscine binding with a Ki value of 0.54 nM. Only bromocriptine was relatively alpha 1-selective with a Ki against [3H]prazosin binding of 18 nM and against [3H]rauwolscine binding of 120 nM. The results indicate that the ergot derivatives tested display a marked affinity for alpha-adrenoceptors and that their actions at this receptor class should be considered when interpreting their pharmacological activity in vivo.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004873:Ergolines / Q000494:pharmacology; D004876:Ergot Alkaloids / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008090:Lisuride / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects*; D015016:Yohimbine / Q000378:metabolism
D004873:Ergolines; D004876:Ergot Alkaloids; D011942:Receptors, Adrenergic, alpha; C031648:etisulergine; D015016:Yohimbine; D008090:Lisuride; D011224:Prazosin