Selectivity of rilmenidine for the nucleus reticularis lateralis, a ventrolateral medullary structure containing imidazoline-preferring receptors

Neuronal metabolic activity was studied by in vivo electrochemistry in two brain areas of the anesthetized rat: the nucleus reticularis lateralis (NRL) region of the ventrolateral medulla oblongata - site of the hypotensive action of clonidine-like imidazolines - and the locus coeruleus (LC), which is involved in the sedative effect of these drugs. Hypotensive doses of i.v. rilmenidine (0.3 and 1.5 mg/kg), which is structurally related to clonidine, induced a dose-related inhibition of the metabolic activity of catecholaminergic neurons in the NRL region whereas higher doses (50-fold) were required to inhibit the activity of the catecholaminergic neurons in the locus coeruleus. On the other hand azepexole, another centrally acting antihypertensive drug that is not structurally related to the imidazolines failed to inhibit the neuronal metabolic activity of the NRL region when administered i.v. in hypotensive doses (1 mg/kg). Taken together, these findings suggest that the central hypotensive action of clonidine-like drugs requires the imidazoline structure or pharmacologically compatible compounds like rilmenidine. Our results also show that rilmenidine is twice as selective as clonidine for the NRL region, which contains imidazoline-preferring receptors, compared with the LC, which contains mainly alpha 2-adrenoceptors. In conclusion, this study provides a functional confirmation of the dissociation between the therapeutic (hypotensive) and untoward (sedative) effects of rilmenidine.