title: Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex.
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Hirosaki, 036-8562, Hirosaki, Japan.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Takuya
authors.initials: T
authors.lastname: Murakami
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawata
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kamata
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: 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
chemical_list: D015220:Calcium Channels; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide; D000109:Acetylcholine