Iontophoretic studies on rat hippocampus with some novel GABA antagonists.
Twelve substances which appear to be GABA antagonists, judging by their ability to reverse the inhibitory effect of GABA on 35S-TBPS binding to rat brain membranes, were tested iontophoretically on population spikes in the rat hippocampus. Eight of them, including seven which completely reversed the inhibitory action of GABA on 35S-TBPS binding, caused a marked enhancement of population spikes, with slow onset and long duration and they antagonized the inhibition of population spikes by GABA. These effects were similar to those produced by bicuculline. Electrophysiologically, the most potent of the "complete reversers" were bathophenanthroline disulfonate and brucine. In vitro, amoxapine and brucine most effectively reversed the inhibitory action of GABA on 35S-TBPS binding. Of the five substances which only partly reversed the inhibitory effect of GABA on 35S-TBPS binding, four depressed the population spikes and potentiated the inhibitory action of GABA. The fifth "partial reverser", pipazethate, potently increased the population spikes, like the "complete reversers". Although other interpretations are possible the results are consistent with the existence of several GABA-A receptor types in brain, only some of which are blocked by certain partial reversers.
D000200:Action Potentials / Q000187:drug effects; D000657:Amoxapine / Q000494:pharmacology; D000818:Animals; D001581:Benzothiadiazines; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D006624:Hippocampus / Q000502:physiology*; D007478:Iontophoresis; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D013331:Strychnine / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001581:Benzothiadiazines; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D010618:Phenanthrolines; D013843:Thiazines; C017049:bathophenanthroline disulfonic acid; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; D013331:Strychnine; C016064:pipazethate; D000657:Amoxapine