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Participation of Imidazoline Receptors and Alpha 2− ‐Adrenoceptors in the Central Hypotensive Effects of Imidazoline‐Like Drugs
Author(s) -
BOUSQUET P.,
BRUBAN V.,
SCHANN S.,
GRENEY H.,
EHRHARDT J. D.,
DONTENWILL M.,
FELDMAN J.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09369.x
Subject(s) - imidazoline receptor , alpha (finance) , alpha 2 adrenergic receptor , pharmacology , adrenergic receptor , rilmenidine , clonidine , receptor , chemistry , endocrinology , medicine , agonist , biochemistry , construct validity , nursing , patient satisfaction
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 I 1 Rs ( K i = 5.10 −7 M ) but roughly not to α 2 ‐adrenoceptors (A 2 Rs) ( K i >10 −5 M ), causes hypotension when injected alone into the brainstem. As far as hybrid drugs, that is, those with mixed binding profiles (I 1 /α 2 ), 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 A 2 Rs antagonist, blocks the hypotensive effect of hybrids but usually in a noncompetitive manner. Mutation of A 2 Rs prevented the hypotensive effects of drugs highly selective for A 2 Rs, 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 A 2 Rs; and (3) requires integrity of A 2 Rs along the sympathetic pathways.