Classification of some GABA antagonists with regard to site of action and potency in slices of rat cuneate nucleus

doi:10.1016/0014-2999(82)90080-2

European Journal of Pharmacology

Volume 80, Issue 4, 4 June 1982, Pages 347-358

https://doi.org/10.1016/0014-2999(82)90080-2 Get rights and content

Abstract

Compounds reported to be GABA antagonists have been studied quantitatively on dorsal funiculus fibres and terminals in the rat cuneate nucleus in vitro. The potencies of the antagonists against the GABA analogue muscimol were determined as pA₂ values. Distinction was made between three different sites of antagonist action within the GABA receptor and ionophore complex. Competitive antagonists, presumed to act at the GABA receptor, and their pA₂ values were bicuculline (5.98), bicuculline methochloride (5.88), strychnine (5.29) and tubocurarine (4.95). Antagonists which were not competitive and acted predominantly at the ‘picrotoxin site’ on the ionophore were picrotoxin (6.19), picrotoxinin (6.03), isopropylbicyclophosphate (5.82) and leptazol (2.89). A third type of antagonism was shown by frusemide. Attention is drawn to the picrotoxin site and its likely importance in the regulation of GABA-mediated inhibition by drugs.

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Classification of some GABA antagonists with regard to site of action and potency in slices of rat cuneate nucleus

Abstract

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Comp. Biochem. Physiol.

Neuroscience Lett.

Neuropharmacol.

Brain Res.

Neuropharmacol.

Neuropharmacol.

European J. Pharmacol.

The pharmacon-receptor-effector concept

Quantitative Aspects of Chemical Pharmacology

Depolarizing actions of γ-aminobutyric acid and related compounds on rat superior cervical ganglion in vitro

Br. J. Pharmacol.

t-Butylbicyclophosphate: a convulsant and GABA antagonist more potent than bicuculline

Br. J. Pharmacol.

Antagonism of inhibitory amino acid action by tubocurarine

Br. J. Pharmacol.

Substrate specificity of [3H]muscimol binding to a particulate fraction of a neuron-enriched culture of embryonic rat brain

J. Neurochem.

Characterization and ionic basis of GABA-induced depolarization recorded in vitro from cat primary afferent neurons

J. Physiol. (London)

Gamma-aminobutyric acid binding in mammalian brain: receptor-like specificity of sodium-independent sites

J. Neurochem.

Interactions of GABA antagonists on the isolated frog spinal cord

Br. J. Pharmacol.

Antagonism of GABA by picrotoxin in the feline cerebral cortex

Br. J. Pharmacol.

Convulsive properties of d-tubocurarine and cortical inhibition

Nature (London)

Substrate specificity of [³H]muscimol binding to a particulate fraction of a neuron-enriched culture of embryonic rat brain