Pantoyl-gamma-aminobutyric acid facilitates cholinergic function in the central nervous system.
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.
Nakahiro
M
M
Fujita
N
N
Fukuchi
I
I
Saito
K
K
Nishimura
T
T
Yoshida
H
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D011963:Receptors, GABA-A; C016030:pantogab; D010205:Pantothenic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine