Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine
Autore:
Witkin, JM; Gasior, M; Heifets, B; Tortella, FC;
Indirizzi:
NIDA,DDrug Dev Grp, Behav Neurosci Branch, Addict Res Ctr,NIH, Baltimore, M NIDA Baltimore MD USA 21224 osci Branch, Addict Res Ctr,NIH, Baltimore, M WalterropharmacolMed Ctr, Walter Reed Army Inst Res, Div Neurosci, Dept Neu Walter Reed Army Med Ctr Washington DC USA 20307 , Div Neurosci, Dept Neu
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 289, anno: 1999,
pagine: 703 - 711
SICI:
0022-3565(199905)289:2<703:AEONAA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA RECEPTOR ANTAGONISTS; DISCRIMINATIVE STIMULUS; BEHAVIORAL PHARMACOLOGY; PHENCYCLIDINE-LIKE; RAT-BRAIN; DIZOCILPINE; SITE; MEMANTINE; TOXICITY; AFFINITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Witkin, JM NIDA,Shock Dev Grp, Behav Neurosci Branch, Addict Res Ctr,NIH, 5500 Nathan NIDA 5500 Nathan Shock Dr Baltimore MD USA 21224 H, 5500 Nathan
Citazione:
J.M. Witkin et al., "Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine", J PHARM EXP, 289(2), 1999, pp. 703-711

Abstract

Convulsions associated with cocaine abuse can be life threatening and resistant to standard emergency treatment. Cocaine (75 mg/kg, i.p.) produced clonic convulsions in similar to 90% of male, Swiss-Webster mice. A variety of clinically used antiepileptic agents did not significantly protect against cocaine convulsions (e.g., diazepam and phenobarbital). Anticonvulsants in clinical practice that did significantly protect against convulsion did so only at doses with significant sedative/ataxic effects (e.g., clonazepam and valproic acid). In contrast, functional N-methyl-D-aspartate (NMDA) antagonists all produced dose-dependent and significant protection against theconvulsant effects of cocaine. Anticonvulsant efficacy was achieved by blockade of both competitive and noncompetitive modulatory sites on the NMDA receptor complex. Thus, competitive antagonists, ion-channel blockers, polyamine antagonists, and functional blockers of the strychnine-insensitive glycine modulatory site all prevented cocaine seizures. The role of NMDA receptors in the control of cocaine-induced convulsions was further strengthenedby the positive correlation between the potencies of noncompetitive antagonists or competitive antagonists to block convulsions and their respective affinities for their specific binding sites on the NMDA receptor complex. Although some NMDA blockers produced profound behavioral side effects at efficacious doses (e.g., noncompetitive antagonists), others (e.g., some low-affinity channel blockers, some competitive antagonists, and glycine antagonists) demonstrated significant and favorable separation between their anticonvulsant and side effect profiles. The present results provide the most extensive evidence to date identifying NMDA receptor blockade as a potential strategy for the discovery of agents for clinical use in averting toxic sequelae from cocaine overdose. Given the literature suggesting a role for these drugs in other areas of drug abuse treatments, NMDA receptor antagonistssit in a unique position as potential therapeutic candidates.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:30:27