Cardiovascular and central nervous system effects of rilmenidine (S 3341) in rats

Rilmenidine (S 3341) is a new alpha 2 agonist, with antihypertensive properties. Pharmacologic data concerning its hemodynamic and central nervous system effects in the rat are described in this report. In the anesthetized or conscious spontaneously hypertensive rat, rilmenidine was found effective and potent as an antihypertensive agent, lowering blood pressure in a dose-dependent manner after intravenous and oral administration. These effects are related to a reduction in sympathetic tone as seen by the decrease in plasma catecholamines induced by rilmenidine in the spontaneously hypertensive rat. Studies in the normotensive pithed rat (electrical stimulation and adrenalectomization) confirmed the presynaptic alpha 2-stimulating properties of rilmenidine and suggested that a component of the antihypertensive activity of rilmenidine could be exerted through these peripheral receptors. A study of the central effects of rilmenidine was performed using classic neuropharmacologic tests. No effect was observed on the pentobarbitone-induced sleeping time in the rat. Rilmenidine caused only a minimal and non-dose-dependent inhibition of the righting reflex in the chick. In the rat, rilmenidine did not decrease the motor activity at concentrations up to 50 times higher than the antihypertensive dose. These results confirmed the contrast between rilmenidine and clonidine and suggest that a dissociation between sedative and antihypertensive effects could occur with rilmenidine.