Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644: comparison with the effects of dextrorphan.
Behav Brain Res
; 120(2): 169-75, 2001 May.
Article
em En
| MEDLINE
| ID: mdl-11182165
ABSTRACT
BAY k-8644 (an L-type Ca(2+) channel agonist of the dihydropyridine class) is recognized as a potent convulsant agent. In this study, we used BAY k-8644 to explore the effects of dextromethorphan (DM) and its major metabolite, dextrorphan (DX), on the (pro)convulsant activity regulated by calcium channels. BAY k-8644 (2 mg/kg, s.c) potentiated seizures induced in rats by kainic acid (KA) (10 mg/kg, i.p.). DM appears more efficacious than DX in attenuation of KA-induced seizures. The anticonvulsant effect of a low dose (12.5 mg/kg, s.c.) of DM was reversed by BAY k-8644 (2 mg/kg) challenge. In contrast, BAY k-8644 (1 or 2 mg/kg) did not significantly affect an anticonvulsant effect from a higher dose (25 mg/kg) of either DM or DX. Intracerebroventricular injection of BAY k-8644 (37.5 microg) significantly induced seizures in mice. DM (12.5 or 25 mg/kg) pretreatment more significantly attenuated seizures evoked by BAY k-8644 than did DX (12.5 or 25 mg/kg). Furthermore, seizure activity induced by KA or BAY k-8644 was consistent with respective activator protein-1 DNA binding activity of the hippocampus. Therefore, our results suggest that the anticonvulsant effects of the morphinans involve, at least in part, the L-type calcium channel. They also suggest that DM is a more potent anticonvulsant than DX in the KA and BAY k-8644 seizure models.
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Base de dados:
MEDLINE
Assunto principal:
Convulsões
/
Agonistas dos Canais de Cálcio
/
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)
/
Fármacos Neuroprotetores
/
Agonistas de Aminoácidos Excitatórios
/
Dextrometorfano
/
Dextrorfano
/
Ácido Caínico
/
Anticonvulsivantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article