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Titolo:
Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs
Autore:
Damaj, MI; Slemmer, JE; Carroll, FI; Martin, BR;
Indirizzi:
Virginiachmond,wealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Ri Virginia Commonwealth Univ Richmond VA USA 23298 Pharmacol & Toxicol, Ri Res Triangle Inst, Res Triangle Pk, NC 27709 USA Res Triangle Inst Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 289, anno: 1999,
pagine: 1229 - 1236
SICI:
0022-3565(199906)289:3<1229:PCONIW>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACETYLCHOLINE-RECEPTOR SUBTYPES; LIGAND-BINDING; RAT-BRAIN; DOPAMINE; SYNAPTOSOMES; AMPHETAMINE; RELEASE; MICE; NOREPINEPHRINE; ANTAGONISTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Damaj, MI VirginiaxCommonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Bo Virginia Commonwealth Univ Box 980613 Richmond VA USA 23298 , Bo
Citazione:
M.I. Damaj et al., "Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs", J PHARM EXP, 289(3), 1999, pp. 1229-1236

Abstract

Cocaine and a number of 3 beta-phenyltropane cocaine analogs were investigated for their potential to block various pharmacological effects of nicotine in animals. They blocked the antinociceptive effect of nicotine in the tail-flick test after systemic administration in a dose-dependent manner. Similarly, cocaine was also able to block nicotine-induced motor impairment in mice. Furthermore, cocaine blocked nicotine-induced seizures at a lower potency than for antinociception, but failed to block nicotine's effect on body temperature and drug discrimination. The antagonistic potencies of the 3 beta-phenyltropane cocaine analogs were not correlated with their affinity for monoamines transporters. Additionally, bupropion, nomifensin, GBR 12909, and nisoxetine, but not methylphenidate and fluoxetine, blocked nicotine-induced antinociception; however, their antagonistic potencies were unrelated to their affinities for the transporters. Taken together, these results suggest that the mechanism of cocaine's antagonistic activity is not related to its binding and uptake of inhibition on monoamine neurotransporters. The failure of lidocaine and procaine to antagonize nicotine's effects in the tail-flick assay rules out local anesthetic effects. In addition, cocaine blocked differentially the response of nicotine in the oocyte receptor expression system for the alpha(4)beta(2) and alpha(3)beta(2) subtypes in a dose-dependent manner. Our results suggest that cocaine is a noncompetitivenicotinic antagonist with some selectivity for neuronal nicotinic receptorsubtypes. Our studies also demonstrate that 3 beta-phenyltropane analogs constitute a new class of nicotinic antagonists. Elucidation of the mechanism of action of this new class of antagonists may provide an explanation forthe effectiveness of agents such as bupropion for the treatment of smokingcessation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 17:03:20