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STUDIES ON SOME para ‐SUBSTITUTED CLONIDINE DERIVATIVES THAT EXHIBIT AN α‐ADRENOCEPTOR STIMULANT ACTIVITY
Author(s) -
LECLERC G.,
ROUOT B.,
SCHWARTZ J.,
VELLY J.,
WERMUTH C.G.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10902.x
Subject(s) - clonidine , chemistry , agonist , medicine , endocrinology , stimulant , adrenergic , alpha (finance) , pharmacology , receptor , biochemistry , construct validity , nursing , patient satisfaction
1 α‐Adrenoceptor stimulant activity was determined for noradrenaline (NA), clonidine and a series of para ‐substituted derivatives of clonidine on rat aortic strips, a rat brain synaptosome preparation, and anaesthetized pithed rats. The effects on the blood pressure of intraventricular (i.c.v.) injections of para ‐aminoclonidine were also determined in anaesthetized rats. 2 Para ‐substituted derivatives of clonidine (amino‐, diethylamino‐, ethylamino‐, acetamido‐, bromoacetamido‐, N ‐chloroethyl‐ N ‐methyl‐amino and N ‐β‐chloroethyl‐ N ‐methylaminomethyl‐) retain α‐adrenoceptor stimulant activity. 3 pD 2 values determined on rat aortic strips were 11.2, 7.67 and 9.05 respectively for para ‐aminoclonidine, clonidine and noradrenaline. The K i values of these agents, determined on a rat brain synaptosomal preparation with a radioreceptor assay using [ 3 H]‐clonidine as ligand, were 1.3, 8.0 and 23 n m respectively for para ‐aminoclonidine, clonidine and NA. When given by i.c.v. injection in rats, para ‐aminoclonidine lowered the blood pressure. 4 N ‐β‐chloroethyl‐ N ‐methylaminomethylclonidine is an alkylating agent with an unusual agonist activity. It elicits contractions of the rat aorta that persist despite repeated washing. 5 α‐Adrenoceptor affinities are discussed in relation to their structural features.