DJ-7141, a new alpha-2 agonist with only a mild hypotensive action.
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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C049769:DJ 7141; D003000:Clonidine; D009638:Norepinephrine