Central presynaptic alpha 2-autoreceptors are involved in the blood pressure-lowering effect of moxonidine.

The alpha-adrenoceptor-mediated effects of the newly developed antihypertensive drug moxonidine and of clonidine were compared in four in vitro models and in anesthetized rabbits. Inhibition of the electrically induced twitch response in the isolated rat vas deferens by moxonidine and clonidine (pEC50 values 7.8 and 8.5) was counteracted by yohimbine. The maximum degree of inhibition obtained with both drugs was identical. The contractile response of the rat anococcygeal muscle to moxonidine and clonidine (pEC50 6.2 and 6.9) was antagonized by prazosin. The maximum degree of contraction obtained with moxonidine was similar in degree to that of phenylephrine, whereas that of clonidine was lower. Moxonidine and clonidine inhibited the electrically evoked [3H]norepinephrine (NE) overflow in strips of rabbit pulmonary artery (pEC50 7.1 and 6.6) and in rat brain cortex slices (pEC50 6.9 and 7.7); the effect of moxonidine was counteracted by rauwolscine. After intracisternal injection in anesthetized rabbits, moxonidine lowered blood pressure (BP) more potently than did clonidine. Intracisternal pretreatment of rabbits with 6-hydroxydopamine strongly attenuated the hypotensive effect of moxonidine without affecting that of clonidine. The hypotensive effect of moxonidine was abolished by pretreatment with reserpine and alpha-methyl-p-tyrosine (alpha-MPT). In conclusion, in isolated tissues of the rat, moxonidine is as selective as clonidine as an alpha-adrenoceptor agonist. The hypotensive effect of moxonidine, unlike that of clonidine, appears to involve central presynaptic alpha 2-autoreceptors in large part.