Analysis of the receptor involved in the central hypotensive effect of rilmenidine and moxonidine

Research paper by Christina Bock, Nathalie Niederhoffer, B. Szabo

Indexed on: 01 Apr '99Published on: 01 Apr '99Published in: Naunyn-Schmiedeberg's Archives of Pharmacology


The aim of this study was to determine whether α2-adrenoceptors or imidazoline I1-receptors are responsible for the central sympathoinhibition produced by rilmenidine and moxonidine, two clonidine-like antihypertensive drugs. Rilmenidine and moxonidine were compared with the indirectly acting α2-adrenoceptor agonist α-methyldopa. Three antagonists were used. Yohimbine and SK & F86466 were used as selective α2-adrenoceptor antagonists. They were compared with efaroxan which is also an α2-adrenoceptor antagonist, but, in addition, possesses affinity for imidazoline I1-receptors. According to some but not all studies, the affinity of efaroxan for I1-receptors is much higher than its affinity for α2-adrenoceptors.Drugs were administered into the cisterna cerebellomedullaris of conscious rabbits by a catheter implanted previously under halothane anaesthesia. Rilmenidine (10 μg kg–1), moxonidine (0.3 μg kg–1) and α-methyldopa (0.4 mg kg–1) lowered blood pressure and the plasma noradrenaline concentration; the degree of sympathoinhibition produced by the three agonists was very similar. When injected after the agonists, efaroxan (0.1–14 μg kg–1; cumulative doses), yohimbine (0.4–14 μg kg–1) and SK & F86466 (0.4–44 μg kg–1) counteracted the effects of the agonists on blood pressure and the plasma noradrenaline concentration. Efaroxan was about tenfold more potent than yohimbine and SK & F86466 at antagonizing the hypotensive effects of α-methyldopa. Similarly, efaroxan was two- to tenfold more potent than yohimbine and SK & F86466 against rilmenidine and moxonidine. Finally, efaroxan was about as potent against α-methyldopa as against rilmenidine and moxonidine.The results confirm previous observations that selective α2-adrenoceptor antagonists are capable of completely antagonizing effects of rilmenidine and moxonidine. The effects of the α2-adrenoceptor antagonist with an additional high affinity for imidazoline I1-receptors, efaroxan, can also be explained by blockade of α2-adrenoceptors. Efaroxan was more potent against rilmenidine and moxonidine than the selective α2-adrenoceptor antagonists. This was probably due to the fact that the affinity of efaroxan for α2-adrenoceptors is higher than the affinity of yohimbine and SK & F86466, since efaroxan was also the most potent of the three antagonists against the indirectly acting α2-adrenoceptor agonist α-methyldopa. The observation that efaroxan was equally potent against rilmenidine and moxonidine and against α-methyldopa suggests that the same receptors were involved in the effects of the three agonists, α2-adrenoceptors; this observation is not compatible with the high I1/α2 selectivity of efaroxan and the hypothesis that rilmenidine and moxonidine activate I1-receptors, whereas α-methyldopa activates α2-adrenoceptors. Thus, the data do not indicate involvement of I1 imidazoline receptors in the central sympathoinhibition elicited by ril-menidine and moxonidine in rabbits. It is likely that ril-menidine and moxonidine produce sympathoinhibition by activating the same receptors which are activated by the indirectly acting catecholamine α-methyldopa, namely α2-adrenoceptors.