Studies on some para-substituted clonidine derivatives that exhibit an alpha-adrenoceptor stimulant activity.
1 alpha-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-beta-chloroethyl-N-methylaminomethyl-) retain alpha-adrenoceptor stimulant activity. 3 pD2 values determined on rat aortic strips were 11.2, 7.67 and 9.05 respectively for para-aminoclonidine, clonidine and noradrenaline. The Ki values of these agents, determined on a rat brain synaptosomal preparation with a radioreceptor assay using [3H]-clonidine as ligand, were 1.3, 8.0 and 23 nM respectively for para-aminoclonidine, clonidine and NA. When given by i.c.v. injection in rats, para-aminoclonidine lowered the blood pressure. 4 N-beta-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 alpha-Adrenoceptor affinities are discussed in relation to their structural features.
D000316:Adrenergic alpha-Agonists; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D003000:Clonidine