Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide

• Published in: Canadian journal of physiology and pharmacology 2005-06, Vol.83 (6), p.509-515
• Main Authors: Nammi, Srinivas, Boini, Krishna Murthy, Koppula, Sushruta, Sreemantula, Satyanarayana
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Antihypertensive Agents - adverse effects; Antihypertensive Agents - pharmacology; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Body Temperature - drug effects; Dose-Response Relationship, Drug; Drugs; Female; General pharmacology; Hypertension; Immobility Response, Tonic - drug effects; Male; Medical sciences; Medical treatment; Mice; Motor Activity - drug effects; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Rats; Rats, Wistar; Reserpine - adverse effects; Reserpine - analogs & derivatives; Reserpine - pharmacology; Side effects
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y05-039

Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action. However, its use has been reduced because of its sedative and extra pyramidal symptoms. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine, was synthesized and pharmacologically evaluated in rats and mice for its central (barbiturate hypnosis, spontaneous motor activity, body temperature, and avoidance of conditioned response) and peripheral actions (blood pressure) in comparison with reserpine. The results indicate that reserpine produced a dose-dependent depression of the central nervous system. RMI at doses equal to and double the equimolar doses of reserpine did not produce any behavioural changes compared with control animals. Nevertheless, both reserpine and RMI were found to produce dose-dependent reduction in the blood pressure of anaesthetized rats, although only at higher doses of RMI, indicating that quaternization of reserpine not only attenuated the entry of RMI into the central nervous system, but also reduced its access to the target tissue in the periphery. It is speculated that the hypotensive actions of RMI may also be due to peripheral depletion of catecholamines. Key words: resperine methiodide (RMI), reserpine, behaviour, blood pressure, mice, rats.