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Pantoyl-gamma-aminobutyric acid (P-GABA) administered i.p. inhibited scopolamine- and atropine-induced locomotor activities in mice, but did not inhibit methamphetamine- and apomorphine-induced locomotor activities. In radiolabeled ligand binding experiments, P-GABA did not inhibit the bindings of [3H]quinuclidinyl benzilate, [3H]spiroperidol and [3H]apomorphine to rat brain membranes, but inhibited that of [3H]muscimol. GABA and P-GABA enhanced K+ (25 mM)-induced release of [3H]acetylcholine from slices of the cerebral cortex and hippocampus dose-dependently, and their effects were antagonized by bicuculline but not by tetrodotoxin. These results suggest that P-GABA binds to GABA receptors causing enhanced cholinergic neurotransmission in the central nervous system. The results are discussed in relation to the clinical use of P-GABA in treatment of Alzheimer's disease and senile dementia of the Alzheimer type.
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