Anticonvulsant doses of carbamazepine increase hippocampal extracellular serotonin in genetically epilepsy-prone rats: dose response relationships.
The antiepileptic drug carbamazepine produces dose related anticonvulsant effects in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models. Carbamazepine releases serotonin as part of the pharmacodynamic action by which it suppresses convulsions in GEPRs and it releases serotonin in non-epileptic Sprague-Dawley rats. The two strains which make up the GEPR seizure model (moderate seizure GEPR-3s and severe seizure GEPR-9s) experience anticonvulsant effects in response to different doses of carbamazepine (GEPR-3 ED50 = 25 mg/kg; GEPR-9 ED50 = 3 mg/kg). The present study determined that carbamazepine produces a dose related increase in extracellular serotonin in each of the two GEPR strains. The doses of carbamazepine required to increase extracellular serotonin are similar to the doses required for an anticonvulsant effect in each of the strains. This result provides further support for the hypothesis that release of serotonin by carbamazepine is an important part of the pharmacodynamic action by which this drug suppresses seizures.
Dailey
J W
JW
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61656, USA. jwd@uic.edu
Reith
M E
ME
Yan
Q S
QS
Li
M Y
MY
Jobe
P C
PC
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D000927:Anticonvulsants; D012701:Serotonin; D002220:Carbamazepine