Participation of Imidazoline Receptors and Alpha2−-Adrenoceptors in the Central Hypotensive Effects of Imidazoline-Like Drugs
Article first published online: 6 FEB 2006
Annals of the New York Academy of Sciences
How to Cite
BOUSQUET, P., BRUBAN, V., SCHANN, S., GRENEY, H., EHRHARDT, J. D., DONTENWILL, M. and FELDMAN, J. (1999), Participation of Imidazoline Receptors and Alpha2−-Adrenoceptors in the Central Hypotensive Effects of Imidazoline-Like Drugs. Annals of the New York Academy of Sciences, 881: 272–278. doi: 10.1111/j.1749-6632.1999.tb09369.x
- Issue published online: 6 FEB 2006
- Article first published online: 6 FEB 2006
ABSTRACT: The central hypotensive effect of imidazoline-like drugs (IMs) involves non-adrenergic imidazoline receptors (IRs). IMs cause hypotension irrespective of their affinity and selectivity for one or the other α-adrenoceptor subtypes. LNP 509, which binds to I1Rs (Ki= 5.10−7 M) but roughly not to α2-adrenoceptors (A2Rs) (Ki >10−5 M), causes hypotension when injected alone into the brainstem. As far as hybrid drugs, that is, those with mixed binding profiles (I1/α2), are concerned, a significant correlation was reported between their central hypotensive effect and their affinity for IRs. Imidazoline antagonists such as idazoxan competitively antagonized the centrally induced hypotensive effect of IMs. Yohimbine, an A2Rs antagonist, blocks the hypotensive effect of hybrids but usually in a noncompetitive manner. Mutation of A2Rs prevented the hypotensive effects of drugs highly selective for A2Rs, but also that of hybrids such as clonidine. These data indicate that triggering of the hypotensive effects of IMs (1) needs implication of IRs; (2) appears to be facilitated by additional activation of A2Rs; and (3) requires integrity of A2Rs along the sympathetic pathways.