Head G A, Sannajust F
Baker Medical Research Institute, Prahran, Victoria, Australia.
Fundam Clin Pharmacol. 1992;6 Suppl 1:31S-34S. doi: 10.1111/j.1472-8206.1992.tb00139.x.
The present paper summarizes our studies concerning the involvement of imidazoline and alpha 2-adrenoceptors in the cardiovascular actions of centrally acting drugs rilmenidine, clonidine and methyldopa. We have found that they produce very similar cardiovascular autonomic effects which relate directly to the function of central monoamine neurotransmitters. They mimic certain elements of the noradrenergic neuron system in the central nervous system, in particular the brainstem actions which involve hypotension, bradycardia and resetting of the baroreceptor heart rate reflex. By contrast they turn off serotonergic pathways that are pressor, produce tachycardia and inhibit the baroreceptor heart rate reflex. Recent studies using specific receptors antagonist drugs idazoxan and 2-methoxy-idazoxan indicate that in conscious rabbits the imidazoline receptor actions of rilmenidine is of primary importance at doses which would be considered clinically relevant. We further conclude that the alpha 2-adrenoceptors and the imidazoline receptors are likely to be located in series i.e. along the same cardiovascular autonomic pathways in the brainstem but presumably at different sites.
本文总结了我们关于咪唑啉和α2-肾上腺素能受体参与中枢作用药物利美尼定、可乐定和甲基多巴心血管作用的研究。我们发现它们产生非常相似的心血管自主效应，这些效应直接与中枢单胺类神经递质的功能相关。它们模拟中枢神经系统中去甲肾上腺素能神经元系统的某些元素，特别是涉及低血压、心动过缓和压力感受器心率反射重置的脑干作用。相比之下，它们关闭了具有升压作用的5-羟色胺能通路，产生心动过速并抑制压力感受器心率反射。最近使用特异性受体拮抗剂药物咪唑克生和2-甲氧基-咪唑克生的研究表明，在清醒兔中，利美尼定的咪唑啉受体作用在临床相关剂量下至关重要。我们进一步得出结论，α2-肾上腺素能受体和咪唑啉受体可能串联定位，即在脑干中沿相同的心血管自主通路，但可能位于不同部位。
