PMID: 8968367Dec 1, 1996Paper

RJR-2403: a nicotinic agonist with CNS selectivity II. In vivo characterization

The Journal of Pharmacology and Experimental Therapeutics
P M LippielloA C Collins

Abstract

We have evaluated the physiological and behavioral effects of the CNS-selective nicotinic agonist (E)-N-methyl-4-(3-pyridinyl) -3-butene-1-amine (RJR-2403) using a number of different methods, including 1) reversal of pharmacologically induced amnesia in a step-through passive avoidance paradigm, 2) radial arm maze performance in rats with chemically induced brain lesions, 3) changes in HR and blood pressure in rats and 4) changes in body temperature, Y-maze activity, acoustic startle response and respiration in mice. Our results indicate that RJR-2403 is equal to or better than nicotine on measures of CNS function and cognitive enhancement. Specifically, RJR-2403 significantly improved passive avoidance retention after scopolamine-induced amnesia and enhanced both working and reference memory in rats with ibotenic acid lesions of the forebrain cholinergic projection system in an 8-arm radial maze paradigm. By comparison, RJR-2403 was 15 to 30-fold less potent than nicotine in decreasing body temperature, respiration, Y-maze rears and crosses and acoustic startle response. RJR-2403 also demonstrated greatly reduced cardiovascular effects. RJR-2403 was approximately 10-fold less potent than nicotine in increasing HR and 20-fold ...Continue Reading

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