Effect of a Novel Prolyl Endopeptidase Inhibitor, JTP-4819, on Thyrotropin-Releasing Hormone-Like Immunoreactivity in the Cerebral Cortex and Hippocampus of Aged Rats

We investigated the effects of a novel prolyl endopeptidase inhibitor, JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)-1-pyrrolidinecarboxamide), on thyrotropin-releasing hormone (TRH)-like immunoreactivity (TRH-LI) in the cerebral cortex and hippocampus of aged rat...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1995, Vol.69(3), pp.273-276
Main Authors: Shinoda, Masahiko, Okamiya, Kazuhiro, Toide, Katsuo
Format: Article
Language:English
Subjects:
Aging - metabolism
Animals
Biological and medical sciences
Cerebral Cortex - drug effects
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Hippocampus - drug effects
Hormones. Endocrine system
Immunohistochemistry
JTP-4819
Male
Medical sciences
Pharmacology. Drug treatments
Prolyl endopeptidase
Pyrrolidines - pharmacology
Rats
Rats, Inbred F344
Thyrotropin-Releasing Hormone - drug effects
Thyrotropin-releasing hormone-like immunoreactivity
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Summary:We investigated the effects of a novel prolyl endopeptidase inhibitor, JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)-1-pyrrolidinecarboxamide), on thyrotropin-releasing hormone (TRH)-like immunoreactivity (TRH-LI) in the cerebral cortex and hippocampus of aged rats. The TRH-LI content of both brain regions in aged rats was significantly lower than that in young rats. A single oral dose of JTP-4819 (3 mg/kg) restored the cortical TRH-LI content in aged rats, while doses of 0.3-3 mg/kg restored it in the hippocampus. Repeated oral administration of JTP-4819 at a dose of 1 mg/kg for 21 days produced a significant increase of TRH-LI in the cerebral cortex, while it did so in the hippocampus at doses of 0.3 and 1 mg/kg. Our findings suggest that JTP-4819 may improve the functioning of TRHergic neurons, which deteriorate with senescence.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.69.273