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 language | English |
|---|---|
| Pages (from-to) | 169-175 |
| Number of pages | 7 |
| Journal | Behavioural Brain Research |
| Volume | 120 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2001 Feb 20 |
| Externally published | Yes |
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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
Cite this
Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644 : Comparison with the effects of dextrorphan. / Kim, Hyoung Chun; Ko, Kwang H.; Kim, Won-Ki; Shin, Eun J.; Kang, Kee Seok; Shin, Chan Young; Jhoo, Wang K.
In: Behavioural Brain Research, Vol. 120, No. 2, 20.02.2001, p. 169-175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644
T2 - Comparison with the effects of dextrorphan
AU - Kim, Hyoung Chun
AU - Ko, Kwang H.
AU - Kim, Won-Ki
AU - Shin, Eun J.
AU - Kang, Kee Seok
AU - Shin, Chan Young
AU - Jhoo, Wang K.
PY - 2001/2/20
Y1 - 2001/2/20
N2 - 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.
AB - 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.
KW - Activator protein-1 DNA binding activity
KW - Dextromethorphan
KW - Dextrorphan
KW - Hippocampus
KW - L-type calcium channel, BAY k-8644, Kainic acid
UR - http://www.scopus.com/inward/record.url?scp=0035136857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035136857&partnerID=8YFLogxK
U2 - 10.1016/S0166-4328(00)00372-7
DO - 10.1016/S0166-4328(00)00372-7
M3 - Article
VL - 120
SP - 169
EP - 175
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 2
ER -