Prolongation of gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO).
The effects of 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO), an inhibitor of gamma-aminobutyric acid (GABA) uptake, were examined in the rat hippocampal slice and compared to the actions of the potent GABA uptake inhibitor, cis-4-OH-nipecotic acid. THPO reversibly prolonged GABA-mediated inhibitory postsynaptic potentials (IPSPs) but did not prolong conductance changes evoked by iontophoresed GABA. In contrast, cis-4-OH-nipecotic acid prolonged responses to iontophoresed GABA but had little effect on IPSPs. THPO reduced the intensity of spontaneous epileptiform bursts observed in elevated (8.5 mM) potassium; this effect was absent after addition of 100 microM bicuculline. These results suggest that drugs similar to THPO may be useful for enhancing GABA-mediated inhibition, but that THPO acts by a mechanism distinct from that of the GABA uptake inhibitor, cis-4-OH-nipecotic acid.
D000818:Animals; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D007478:Iontophoresis; D007555:Isoxazoles / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D007555:Isoxazoles; D009557:Nipecotic Acids; D010080:Oxazoles; C026804:4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridin-3-ol; D005680:gamma-Aminobutyric Acid; C047022:4-hydroxynipecotic acid