Y-29794--a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain.
A novel non-peptide prolyl endopeptidase (PPCE) inhibitor, Y-29794, has been identified. Y-29794 selectively and competitively inhibited rat brain PPCE (Ki = 0.95 nM) in a reversible manner. Ex vivo study demonstrated that Y-29794 could penetrate into brain to exhibit dose-dependent and long-lasting inhibition. Furthermore, Y-29794 was found to potentiate the effect of TRH on the release of ACh in the rat hippocampus. These results indicate that Y-29794 is an orally active, potent and specific PPCE inhibitor and should be of value in studies on the physiological role of the enzyme in neuropeptide metabolism especially in memory process.
Nakajima
T
T
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Ono
Y
Y
Kato
A
A
Maeda
J
J
Ohe
T
T
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007659:Ketones / Q000737:chemistry / Q000493:pharmacokinetics*; D000085822:Prolyl Oligopeptidases; D051381:Rats; D012697:Serine Endopeptidases; D013876:Thiophenes / Q000737:chemistry / Q000493:pharmacokinetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014018:Tissue Distribution
D007659:Ketones; D013876:Thiophenes; C077994:Y 29794; D013973:Thyrotropin-Releasing Hormone; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D000109:Acetylcholine