Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex.
To clarify the mechanisms of action of antiepileptic drugs (AEDs), carbamazepine (CBZ) and zonisamide (ZNS), on exocytosis mechanisms, the present study determined the concentration-dependent action of CBZ and ZNS, as well as the interaction between these AEDs and voltage-sensitive Ca(2+) channel (VSCC) activity on basal, Ca(2+)- and K(+)-evoked acetylcholine (ACh) release in frontal cortex of freely moving rat using in vivo microdialysis. Perfusion with therapeutic-relevant concentrations of CBZ and ZNS increased basal ACh release, which was regulated by N-type VSCC predominantly and P-type VSCC weakly, whereas supratherapeutic-relevant concentrations of these AEDs reduced this release. The 3.4 mM Ca(2+)-evoked release, which was regulated by N-type VSCC selectively, but not by P-type VSCC, was increased by therapeutic-relevant concentrations of CBZ and ZNS, whereas this release was reduced by supratherapeutic-relevant concentrations of them. The 50 mM K(+)-evoked release, which was regulated by P-type VSCC predominantly and N-type VSCC weakly, was decreased by CBZ and ZNS, in a concentration-dependent manner. These findings indicate that the interplay between enhancement of basal ACh release and reduction of depolarization-related ACh release in the frontal cortex are at least partially involved in a common mechanism of antiepileptic action between CBZ and ZNS.
Zhu
Gang
G
Department of Neuropsychiatry, School of Medicine, University of Hirosaki, 036-8562, Hirosaki, Japan.
Okada
Motohiro
M
Murakami
Takuya
T
Kawata
Yuko
Y
Kamata
Akihisa
A
Kaneko
Sunao
S
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D002220:Carbamazepine / Q000494:pharmacology*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D000078305:Zonisamide
D015220:Calcium Channels; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide; D000109:Acetylcholine