The effects of pentobarbital and benzodiazepines on GABA-responses in the periphery and spinal cord in vitro.
Pentobarbital and benzodiazepines were compared in their interaction with the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline on GABAA receptor-mediated events. On excised vagal nerves and dorsal roots pentobarbital, in contrast to the benzodiazepines diazepam, lorazepam and flurazepam, was able to enhance GABA-induced depolarizations recorded in the presence of picrotoxin or bicuculline. On hemicord preparations picrotoxin simultaneously depressed the electrically evoked dorsal root-dorsal root potential and enhanced the dorsal root-ventral root potential. Pentobarbital overcame the effects of picrotoxin, whereas diazepam and midazolam were without effect. These results may be explained by the suggestion that the GABA receptors in these test systems are not tightly associated with the benzodiazepine receptor activated by diazepam, lorazepam, midazolam and flurazepam, and correspond to the recently described GABAA2 subdivision of GABA receptors.
Wesselman
J P
JP
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
van Wilgenburg
H
H
Long
S K
SK
D000818:Animals; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001569:Benzodiazepines; D001640:Bicuculline; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid