Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide.
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.
Nammi
Srinivas
S
Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.nammi@rediffmail.com
Boini
Krishna Murthy
KM
Koppula
Sushruta
S
Sreemantula
Satyanarayana
S
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology
D000959:Antihypertensive Agents; D012110:Reserpine