Open AccessDJ-7141, a New Alpha-2 Agonist with Only a Mild Hypotensive Action
Author(s) -
Ikunobu Muramatsu,
Masafumi Oshita,
Shigeki Hashimoto,
Shigeru Kigoshi
Publication year - 1986
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.41.61
Subject(s) - clonidine , prazosin , agonist , guanabenz , vas deferens , chemistry , medicine , endocrinology , postsynaptic potential , alpha (finance) , alpha 2 adrenergic receptor , antagonist , pharmacology , receptor , construct validity , nursing , patient satisfaction
The pharmacological profile of a newly synthesized imidazole derivative, DJ-7141, was examined with special reference to alpha-2 adrenoceptors. In the rat vas deferens and dog mesenteric artery, DJ-7141 at concentrations over 10(-9) M selectively acted on the presynaptic alpha-2 adrenoceptors on the sympathetic nerve terminals and inhibited the contractions induced by electrical transmural stimulation. The potency of DJ-7141 was almost the same as those of clonidine and guanabenz. DJ-7141 also acted on the postsynaptic alpha-2 adrenoceptors to contract the dog saphenous vein. However, no alpha-1 agonist and antagonist actions were found at concentrations showing presynaptic alpha-2 agonist activity. In contrast to DJ-7141, clonidine produced an apparent contraction in the dog mesenteric artery, and the response was inhibited by prazosin. In urethane-anesthetized rats, clonidine at doses ranging from 0.003 mg/kg to 0.03 mg/kg produced a marked and prolonged hypotension, while DJ-7141 at such doses failed to produce a reduction of blood pressure. From these results, it is suggested that, in contrast to clonidine and other alpha-2 agonists, DJ-7141 is a unique alpha-2 agonist which shows high affinity to peripheral alpha-2 adrenoceptors but only a mild hypotensive activity.