Effects of the peptide BCH-325 upon the efficacy of common antiepileptic drugs.
It was shown that BCH-325 (Pro-D-Phe-Pro-Gly), a des-tyrosine derivative of beta-casomorphin, exhibits anticonvulsive effects. In the present study, we combined the peptide with clinically used antiepileptic drugs (phenytoine, carbamazepine, diazepam, phenobarbital, and dipropyl acetate) to investigate possible interactions and, moreover, to draw conclusions concerning the mode of action of BCH-325. There were no interactions with phenytoine and carbamazepine, which might be interpreted to mean that BCH-325 exerted no action on sodium channels. The efficacy of the combinations with the other drugs (diazepam, phenobarbital, dipropyl acetate) was increased. The data suggest that the anticonvulsant effect of BCH-325 might occur by interference with elements of GABA/benzodiazepinergic neurotransmission.
Otto-von-Guericke University Magdeburg, Faculty of Medicine, Institute of Pharmacology and Toxicology, Germany.
A
A
Becker
G
G
Grecksch
B
B
Piönnigs
C
C
Ostner
D000595:Amino Acid Sequence; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D002220:Carbamazepine / Q000008:administration & dosage; D003975:Diazepam / Q000008:administration & dosage; D004347:Drug Interactions; D004723:Endorphins / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D010634:Phenobarbital / Q000008:administration & dosage; D010672:Phenytoin / Q000008:administration & dosage; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014635:Valproic Acid / Q000008:administration & dosage; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D004723:Endorphins; D010446:Peptide Fragments; D015222:Sodium Channels; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; C059556:beta-casomorphin, des-Tyr-; D003975:Diazepam; D010634:Phenobarbital