Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes.

Ergot alkaloids act as (partial) agonists or antagonists at serotonergic, dopaminergic and alpha-adrenergic receptors. In contrast to their affinity at serotonergic (5-HT) and dopaminergic receptor subtypes, only limited information is available concerning their interaction with alpha-adrenoceptor subtypes. This especially holds true for native alpha-adrenoceptors. Therefore, we studied the pharmacological profile of 25 ergolines at alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptors in vascular rings or strips of rat and guinea pig endowed with these receptors. Contractile responses were studied by measurement of isometric tension changes in rat tail artery (alpha(1A), alpha(1B)), guinea pig spleen (alpha(1B)) and rat thoracic aorta (alpha(1D)). The anti-migraine drugs ergotamine and dihydroergotamine, the anti-parkinsonian drug lisuride and the anti-hyperprolactinemic drug terguride behaved as antagonists or low-efficacy partial agonists at all three alpha(1)-adrenoceptor subtypes with nanomolar receptor affinity. Derivatives of these drugs showed lower affinity at alpha(1)-adrenoceptors than the parent compounds. Each individual ergoline derivative tested showed low discriminatory capability at the subtypes, alpha(1A), alpha(1B), alpha(1D). A low discriminatory power between the subtypes (alpha(1A), alpha(1B), alpha(1D)) seems to be a class effect of the ergolines. The nanomolar affinities of ergotamine, dihydroergotamine and lisuride for alpha(1)-adrenoceptors may affect their effectiveness as anti-migraine and anti-parkinsonian drugs, respectively.