The alpha 1- and alpha 2-adrenoceptor selectivity of drugs with potential effects on blood pressure--a radioligand-binding study.
In screening compounds with potential antihypertensive properties, the determination of their relative selectivities for alpha 1- and alpha 2-adrenoceptors is important not only for the elucidation of their mechanisms of action but also, possibly, for the assessment of their potential side-effects. The relative selectivity of a number of drugs for alpha 1- and alpha 2-adrenoceptors was determined by means of radioligand-binding studies. The alpha-adrenoceptor antagonists prazosin and indoramin display selectivities for alpha1-adrenoceptors of about factors 1 000 and 4 000 respectively. The alpha-adrenoceptor agonists clonidine and 2-(3,4-dihydroxyphenylimino)-imidazoline (DPI) display selectivities for alpha 2-adrenoceptors of about factors 200 and 300 respectively. The alpha-adrenoceptor antagonist mianserin displays approximately equal, albeit relatively low, affinities for alpha 1- and alpha 2-adrenoceptors. In view of the distribution of alpha 1- and alpha 2-adrenoceptors in vascular smooth muscle and in the reflex arcs controlling blood pressure, the low incidence of reflex tachycardia associated with the use of prazosin and indoramin can be explained on the basis of their alpha 1-adrenoceptor selectivity. Similarly, the hypertensive crisis which may follow the withdrawal of clonidine can be explained on the basis of a selective alpha 2-adrenoceptor agonistic action. The finding that mianserin has such low affinities for both alpha 1- and alpha 2-adrenoceptors may explain why, at therapeutically effective antidepressant dosages, it is usually devoid of adverse haemodynamic effects.
Offermeier
J
J
van Rooyen
J M
JM
Rossouw
J
J
D000316:Adrenergic alpha-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D007217:Indoramin / Q000378:metabolism / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D007217:Indoramin; D003000:Clonidine; D011224:Prazosin