Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats

BACKGROUND: Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In later years, its use has been reduced because of precipitation of depression and extra pyramidal symptoms due to its central action. In the present investigation, reserpine methonitrate (RMN), a novel quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats while its influence on the blood pressure was measured in anaesthetized rats in comparison with reserpine RESULTS: Reserpine treatment (5 mg/kg) produced a significant increase in the urinary excretion of VMA, 5-HIAA and HVA while RMN at doses of equal to and double the equimolar doses of reserpine (5 and 10 mg/kg) produced significant increase in VMA and 5-HIAA excretion without producing any effect on HVA excretion compared to control animals. Reserpine in the dose range of 0.5 to15 μg/kg produced significant reduction in blood pressure compared to control. RMN was also found to produce significant decrease in blood pressure at doses of 10, 25 and 50 μg/kg body weight in comparison to control. The results indicated peripheral depletion of biogenic amines by RMN without affecting the central stores of the amines. CONCLUSIONS: The present study clearly indicated that the quaternization of reserpine restricts its transfer across the blood-brain barrier and could be the reason for its selective peripheral action. It is also clear that the hypotensive actions of RMN could be due to peripheral depletion of catecholamines.