Abecarnil (
ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboxylate) is a metabolically stable
beta-carboline derivative with potent
anxiolytic and few
sedative and ataxic effects in rodents. The
anticonvulsant and muscle relaxant actions of
abecarnil have been evaluated in mice, rats, gerbils and baboons.
Abecarnil raised the threshold for tonic electroconvulsions in mice after corneal but not after auricular application, had no effect on maximal electroshock-induced tonic convulsions triggered by either method, protected mice against the tonic hindlimb extension in PTZ-,
picrotoxin- and 3-mercaptopropionate-induced
seizures and blocked clonus after PTZ,
DMCM (methyl-4-ethyl-6,7-dimethoxy-9H-pyrido-(3,4-b)-indol-3-carboxylate) and 3-mercaptopropionate.
Abecarnil had no effect on convulsions induced by
bicuculline and
strychnine. Furthermore,
abecarnil blocked kindled
seizures after chronic administration of PTZ and
FG 7142 (beta-carboline-3-carboxylic acid methylamide) and protected mice and rats against limbic convulsions induced by
pilocarpine. Severity and afterdischarge duration of amygdala-kindled
seizures were reduced in rats treated with
abecarnil.
Abecarnil also antagonized selectively convulsions induced by i.c.v. administration of
kainate, but not those triggered by
N-methyl-D-aspartate or
quisqualate. In genetic models of
reflex epilepsy,
abecarnil was effective against sound-induced convulsions in DBA/2 mice, against air blast-induced
generalized seizures in gerbils and against
myoclonus in baboons Papio papio. The
anticonvulsant effect of abecornil in a PTZ seizure model in mice was potentiated by
ethosuximide, whereas no significant potentiation was found with
diazepam,
clonazepam,
diphenylhydantoin,
carbamazepine and
phenobarbital. Electromyographic monitoring in a
etorphine model of
muscle rigidity in rats showed no or little muscle relaxant effect of
abecarnil.(ABSTRACT TRUNCATED AT 250 WORDS)