Search results for "GABA-A Receptor Antagonists"

Effects of clozapine metabolites and chronic clozapine treatment on rat brain GABAA receptors

1996

Abstract Similarly to clozapine, a clozapine metabolite, N -desmethylclozapine, but not clozapine N -oxide, antagonized brain γ-aminobutyric acid type A (GABA A ) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([ 3 H]flunitrazepam) or convulsant ( t -[ 35 S]bicyclophosphorothionate) binding sites of the GABA A receptor. The results thus suggest that the GABA A receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine …

Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone

2010

Abstract The aims of the present study were to investigate, using mouse whole stomach in vitro , the effects of γ-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA A -receptor antagonist, bicuculline, potentiated by phaclofen, GABA B -receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA C -receptor antagonist. Muscimol, GABA A -receptor agonist, mimicked GABA effects inducing relaxation, which was significantly re…

What is the form of muscimol from fly agaric mushroom (Amanita muscaria) in water? An insight from NMR experiment supported by molecular modeling.

2020

ARTYKUŁ Z BADAŃ SPECJALNYCH

The main determinant of furosemide inhibition on GABA(A) receptors is located close to the first transmembrane domain.

1998

Inhibitory GABA(A) receptors are regulated by numerous allosteric modulators, the most receptor-subtype specific of which is furosemide. It recognises receptors of the subunit composition alpha6beta2/3gamma2, restricted to cerebellar granule cells. To locate furosemide's site of action we constructed chimeras of the furosemide-sensitive alpha6 and the furosemide-insensitive alpha1 subunit, and expressed and studied them together with the beta3 and gamma2 subunits in Xenopus oocytes by the two-electrode voltage clamp technique. The inhibition of GABA-induced currents by furosemide mainly depended on a short domain proximal to the first transmembrane region of the alpha6 subunit.

Structure-activity relationship of furosemide-derived compounds as antagonists of cerebellum-specific GABA(A) receptors.

1998

The Na+-K+-2Cl- cotransporter blocker furosemide inhibits gamma-aminobutyric acid (GABA)-gated chloride currents and reverses GABA-mediated inhibition of [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) binding of the cerebellar alpha6 subunit-containing GABA(A) receptors much more potently than the cerebrocortical non-alpha6 subunit-containing receptors. Of the 44 compounds studied, all precursors or derivatives of diuretics, one compound [hydrazinosulfonyl-furosemide (PF 1885)] reversed 5-microM GABA-induced inhibition of [35S]TBPS binding to cerebellar and cerebrocortical receptors. Three other compounds, all of which are structurally closely related to furosemide, were selective antago…

New Therapeutic Aspects in Fulminant Hepatic Failure

1991

GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex

2010

Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the func- tional role of GABAC receptors in radial migration we ana- lyzed the effects of specific GABAA and GABAC receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experi- ments revealed that the GABAA specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABAC specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphos- phinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionot…