Muramatsu I, Oshita M, Hashimoto S, Kigoshi S
Jpn J Pharmacol. 1986 May;41(1):61-8. doi: 10.1254/jjp.41.61.
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.
对新合成的咪唑衍生物DJ - 7141的药理特性进行了研究，特别参考了α-2肾上腺素能受体。在大鼠输精管和犬肠系膜动脉中，浓度超过10(-9)M的DJ - 7141选择性作用于交感神经末梢的突触前α-2肾上腺素能受体，并抑制经壁电刺激诱导的收缩。DJ - 7141的效力与可乐定和胍那苄几乎相同。DJ - 7141还作用于突触后α-2肾上腺素能受体，使犬隐静脉收缩。然而，在显示突触前α-2激动剂活性的浓度下，未发现α-1激动剂和拮抗剂作用。与DJ - 7141不同，可乐定在犬肠系膜动脉中产生明显的收缩，且该反应被哌唑嗪抑制。在乌拉坦麻醉的大鼠中，剂量为0.003mg/kg至0.03mg/kg的可乐定产生显著且持久的低血压，而在此剂量下DJ - 7141未能使血压降低。从这些结果表明，与可乐定和其他α-2激动剂不同，DJ - 7141是一种独特的α-2激动剂，对外周α-2肾上腺素能受体具有高亲和力，但只有轻度的降压活性。
