PMID- 7617141 OWN - NLM STAT- MEDLINE DCOM- 19950823 LR - 20190726 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 34 IP - 2 DP - 1995 Feb TI - Abecarnil enhances GABA-induced currents in acutely isolated cerebellar Purkinje cells. PG - 157-63 AB - The effect of abecarnil, a beta-carboline derivative acting at central gamma-aminobutyric acid (GABAA)/benzodiazepine receptors, on the response to GABA of isolated Purkinje cells acutely dissociated from rat cerebellar slices was studied. Using a rapid superfusion system to apply drugs and whole-cell voltage-clamp recording configuration, abecarnil was found to be of similar efficacy to diazepam (DZP) in enhancing GABA-mediated responses. Abecarnil potentiated GABA-induced chloride currents maximally by 241%, while DZP showed a maximal potentiation of 217%. However, abecarnil was more potent than DZP and exhibited different potentiation kinetics. While the response to DZP was fast and reversible, abecarnil after a 1-3 sec application initially produced only a very small enhancement of the GABA response. The effect then developed gradually even after cessation of abecarnil application, and depended on both abecarnil concentration and exposure time. It is suggested that abecarnil accumulates in the lipid membrane resulting in slow effect kinetics and prolonged presence at the benzodiazepine binding site. Abecarnil is a full agonist at the GABAA/benzodiazepine receptor on Purkinje cell somatic membranes. FAU - Vorobjev, V S AU - Vorobjev VS AD - Brain Research Institute, Academy of Medical Sciences of Russia, Moscow. FAU - Sharonova, I N AU - Sharonova IN FAU - Skrebitsky, V G AU - Skrebitsky VG FAU - Schneider, H H AU - Schneider HH FAU - Stephens, D N AU - Stephens DN LA - eng PT - Journal Article PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Carbolines) RN - 0 (Chloride Channels) RN - 0 (Receptors, GABA) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - IZM1PNJ3JL (abecarnil) RN - Q3JTX2Q7TU (Diazepam) SB - IM MH - Animals MH - Carbolines/*pharmacology MH - Cells, Cultured MH - Chloride Channels/drug effects MH - Diazepam/pharmacology MH - Dose-Response Relationship, Drug MH - Female MH - Male MH - Purkinje Cells/*drug effects MH - Rats MH - Rats, Wistar MH - Receptors, GABA/drug effects MH - Time Factors MH - gamma-Aminobutyric Acid/*pharmacology EDAT- 1995/02/01 00:00 MHDA- 1995/02/01 00:01 CRDT- 1995/02/01 00:00 PHST- 1995/02/01 00:00 [pubmed] PHST- 1995/02/01 00:01 [medline] PHST- 1995/02/01 00:00 [entrez] AID - 002839089400139J [pii] AID - 10.1016/0028-3908(94)00139-j [doi] PST - ppublish SO - Neuropharmacology. 1995 Feb;34(2):157-63. doi: 10.1016/0028-3908(94)00139-j.