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Titolo:
Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice
Autore:
Popik, P; Kozela, E; Danysz, W;
Indirizzi:
Polish Acad Sci, Inst Pharmacol, PL-31343 Krakow, Poland Polish Acad Sci Krakow Poland PL-31343 harmacol, PL-31343 Krakow, Poland Merz & Co GmbH & Co, Dept Pharmacol, D-60318 Frankfurt, Germany Merz & Co GmbH & Co Frankfurt Germany D-60318 D-60318 Frankfurt, Germany
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 4, volume: 361, anno: 2000,
pagine: 425 - 432
SICI:
0028-1298(200004)361:4<425:CANRAM>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRECIPITATED OPIOID WITHDRAWAL; ANALGESIC TOLERANCE; GLYCINE SITE; MK-801; LY274614; BLOCKADE; RATS; DIZOCILPINE; MODULATION; DEPENDENCE;
Keywords:
NMDA antagonist; memantine; dextromethorphan; MRZ 2/579; analgesia; antinociception; tolerance; morphine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Popik, P Polish Acad Sci, Inst Pharmacol, 12 Smetna St, PL-31343 Krakow, Poland Polish Acad Sci 12 Smetna St Krakow Poland PL-31343 akow, Poland
Citazione:
P. Popik et al., "Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice", N-S ARCH PH, 361(4), 2000, pp. 425-432

Abstract

The tail-flick test was used to investigate the effects of chronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan, memantine and MRZ 2/579, on the development and reversal of morphine tolerance in mice in three separate experiments. Experiment 1 investigated the effects of NMDA receptor antagonists on the development of tolerance. Morphine (10 mg/kg for 6 days, twice daily) produced a 5.9-fold rightward shift of the cumulative dose-response curves. Co-administration of dextromethorphan, memantine or MRZ 2/579 between tests 1 and 2 dose-dependently (5-10 mg/kg) inhibited the development of morphine tolerance. In experiment 2,in which the effects on the reversal were investigated, morphine-tolerant mice were treated b.i.d. for an additional 6 days (between tests 2 and 3) with vehicle+vehicle, NMDA receptor antagonist+vehicle, vehicle+morphine or NMDA receptor antagonist+morphine. Morphine-tolerant mice treated with vehicle+vehicle remained morphine tolerant, whereas this residual morphine tolerance was inhibited by administration of all three NMDA antagonists (each 10 mg/kg). Morphine-tolerant mice receiving vehicle+morphine injections demonstrated an unchanged degree of antinociceptive tolerance. In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance. In experiment 3, memantine and MRZ 2/579 (10 mg/kg) inhibited the acute antinociceptive effect of morphine, but dextromethorphan did not. These data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:22:02