Effects of the beta-carboline abecarnil on epileptic activity, EEG, sleep and behavior of rats.
The profile of the anxiolytic beta-carboline isopropyl 6-benzyloxy-4-methoxymethyl beta-carboline-3-carboxylate (abecarnil; ZK 112 119), a partial agonist at benzodiazepine receptors, was determined in two experiments. In the first, abecarnil was given to WAG/Rij rats; these rats generate spontaneously occurring spike-wave discharges and are regarded as a model for absence epilepsy. Effects were measured on epileptic activity, together with those on the spectral content of the background electroencephalograph (EEG), as well as on ongoing behavior. In a second experiment, effects on sleep and behavior were investigated in Wistar rats. It was found that, similarly to classical benzodiazepines, abecarnil possessed a strong antiepileptic character and also changed the background EEG to more high-frequency waves and less spindle activity. It also produced more immobile behavior. Abecarnil induced only small, marginally significant increases in slow-wave sleep while reducing REM sleep as a proportion of total sleep. It also reduced the number of REM periods. These observations are consistent with the proposed partial agonist activity of abecarnil, a drug with interesting therapeutic implications.
Coenen
A M
AM
Department of Psychology, University of Nijmegen, The Netherlands.
Stephens
D N
DN
Van Luijtelaar
E L
EL
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects
D000927:Anticonvulsants; D002243:Carbolines; C062769:abecarnil