L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice.
Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice.L-Histidine, administered at the doses that did not influence the threshold for electroconvulsions (250-500 mg/kg), enhanced by nearly 30% the protective effects of carbamazepine against maximal electroshock-induced seizures. D-Histidine (1000 mg/kg), an inactive isomer of histidine, was without any effect in this regard. L-Histidine (500 mg/kg) also augmented the protective effects of phenytoin. Importantly, the enhancement of the anticonvulsant effects of these antiepileptic drugs produced by L-histidine co-administration was not associated with augmentation of their unwanted effects on memory and motor performance. A pharmacokinetic interaction was also excluded since the free plasma levels of these antiepileptics remained unchanged in the presence of L-histidine. It may be suggested that L-histidine could serve as a beneficial adjuvant for selected antiepileptic drugs.
Kamiński
R M
RM
Isotope Laboratory, Institute of Agricultural Medicine, Lublin, Poland. kamiskr@ninds.nih.gov
Zółkowska
D
D
Kozicka
M
M
Kleinrok
Z
Z
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood; D002220:Carbamazepine / Q000008:administration & dosage* / Q000097:blood; D004357:Drug Synergism; D004597:Electroshock; D006639:Histidine / Q000008:administration & dosage* / Q000097:blood; D051379:Mice; D010672:Phenytoin / Q000008:administration & dosage* / Q000097:blood; D012640:Seizures / Q000097:blood / Q000188:drug therapy*
D000927:Anticonvulsants; D002220:Carbamazepine; D006639:Histidine; D010672:Phenytoin