RT Journal Article
SR Electronic
T1 Antinociceptive and Antiamnesic Properties of the Presynaptic Cholinergic Amplifier PG-9
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 806
OP 816
VO 284
IS 3
A1 Carla Ghelardini
A1 Nicoletta Galeotti
A1 Fulvio Gualtieri
A1 Vittorio Marchese
A1 Cristina Bellucci
A1 Alessandro Bartolini
YR 1998
UL http://jpet.aspetjournals.org/content/284/3/806.abstract
AB The antinociceptive effect of 3α-tropyl 2-(p-bromophenyl)propionate [(±)-PG-9] (10–40 mg kg−1 s.c.; 30–60 mg kg−1 p.o.; 10–30 mg kg−1 i.v.; 10–30 μg/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (±)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (±)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the γ-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3agonist R-(α)-methylhistamine, the D2antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamine1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (±)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (±)-PG-9 (10–40 mg kg−1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg−1 i.p.) and dicyclomine (2 mg kg−1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (±)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1selectivity ratio of 10.2 that might be responsible for the antinociception and the antiamnesic effect induced by (±)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (±)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus. The American Society for Pharmacology and Experimental Therapeutics