Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644: Comparison with the effects of dextrorphan

Hyoung Chun Kim, Kwang H. Ko, Won-Ki Kim, Eun J. Shin, Kee Seok Kang, Chan Young Shin, Wang K. Jhoo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

BAY k-8644 (an L-type Ca2+ 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 μg) 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.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalBehavioural Brain Research
Volume120
Issue number2
DOIs
Publication statusPublished - 2001 Feb 20
Externally publishedYes

Keywords

  • Activator protein-1 DNA binding activity
  • Dextromethorphan
  • Dextrorphan
  • Hippocampus
  • L-type calcium channel, BAY k-8644, Kainic acid

ASJC Scopus subject areas

  • Behavioral Neuroscience

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