Inhibition of photosensitive seizures in man by the beta-carboline, ZK 95962, a selective benzodiazepine receptor agonist.
A single-dose study of the beta-carboline, ZK 95962, on photosensitive generalized paroxysmal activity in the EEG was conducted in 6 patients with primary generalized epilepsy. Four of the patients were newly diagnosed and did not receive any antiepileptic drug or other medication during the study. Two were receiving current therapy with carbamazepine. A double-blind cross-over study with 2 injections of ZK 95962 (20 micrograms/kg body weight repeated 10 min after 1st injection) and 2 placebo injections were carried out in a randomized order, with 4 h intervals between the injections with active drug and placebo. On the day before the trial, the sensitivity range (standardized photosensitivity range, SPR) was determined hourly using flash frequencies of 2, 6, 8, 10, 15, 20, 30 and 40 Hz for 4 sec in ascending and descending order until generalized spikes or spike waves occurred. A significant reduction in photosensitivity was observed 2-12 min after injection of ZK 95962 in all patients, lasting 2-3 h. No change in the SPR was observed after placebo injections. The feelings of uneasiness and myoclonic jerks, provoked by photostimulation, were also abolished by ZK 95962, but not by placebo injections. Side effects, including sedation were not observed. The results suggest that benzodiazepine receptor ligands such as ZK 95962 may be potent antiepileptic drugs.
Møller
A
A
Department of Neurology and Neurophysiology, University Hospital of Hvidovre, Copenhagen, Denmark.
Jensen
L H
LH
Skrumsager
B
B
Blatt-Lyon
B
B
Pedersen
B
B
Dam
M
M
D000293:Adolescent; D000328:Adult; D002243:Carbolines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D002243:Carbolines; D011963:Receptors, GABA-A; C063837:ZK 95962