[Current data on the pharmacology of rilmenidine]

Oral rilmenidine (1 mg/kg/day for 2 weeks) significantly reduces the blood pressure and heart rate of conscious barodenervated dogs. A dose-dependent decrease in blood pressure and heart rate has been demonstrated with intraveinous rilmenidine (0.1 to 1 mg/kg) in pentobarbitone anaesthetised spontaneously hypertensive rats (SHR). Chronic subcutaneous administration of rilmenidine (5 to 15 mg/kg/day) also produces a dose-dependent decrease of these two parameters in conscious SHR. In addition, rilmenidine reduces plasma noradrenaline and the liberation of catecholamines from the adrenal medulla; these actions could contribute to its antihypertensive effect. The hypotensive effect of rilmenidine, clonidine and related molecules, is due to a reduction in sympathetic tone of central or peripheral origin. Although rilmenidine binds to alpha-2 adrenergic receptors, it does not cause sedation in animal models: it does not prolong barbiturate-induced sleep in the mouse and rat at doses of up to 10 mg/kg and does not affect spontaneous locomotor activity in the rat at doses of up to 2.5 mg/kg. The results show a dissociation of the sedative and antihypertensive effects of rilmenadine. The almost complete absence of sedation in animal models may be explained by: as yet unknown properties inhibiting sedation, a preferential peripheral site of action and/or the presence of separate central receptors accounting for the sedative or hypotensive effects. The precise mechanism of the hypotensive effects of rilmenidine is currently under study. The binding of rilmenidine at central "imidazoline receptor" sites responsible for the regulation of the blood pressure could explain its mode of action and why its pharmacological profile is different to that of other centrally acting hypotensive agents.