Pharmacological evidence for lack of central effects of reserpine methonitrate: A novel quaternary analog of reserpine

Background: Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. However, its use was reduced in later years due to its sedative and extrapyramidal symptoms. Objective: The present investigation aimed to synthesize reserpine methonitrate, a quaternary analog of reserpine and evaluate pharmacologically its central and peripheral actions in comparison to reserpine. Methods: The change in behavior of mice and rats after treatment with reserpine or reserpine methonitrate as assessed by their effects on barbiturate hypnosis, spontaneous motor activity, body temperature, avoidance of conditioned response and palpebral closure were considered to be central actions while their influence on the blood pressure of anesthetized rats was measured for their peripheral actions. Results: The results indicate that reserpine produced central depression dose-dependently as determined from the battery of tests on the behavior of mice and rats. Reserpine methonitrate at doses equal to and double the equimolar doses of reserpine did not produce any behavioral changes compared with control animals. Conclusions: Both reserpine and reserpine methonitrate were found to produce a dose-dependent reduction in the blood pressure of anesthetized rats, although with higher doses of reserpine methonitrate indicated that quaternization of reserpine not only attenuated the entry of the analog into the CNS, but also reduced to the target tissue in the periphery.