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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-10-25
|
| pubmed:abstractText |
JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/JTP 4819,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Scopolamine Hydrobromide,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/prolyl oligopeptidase
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
274
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1370-8
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:7562510-Acetylcholine,
pubmed-meshheading:7562510-Aging,
pubmed-meshheading:7562510-Animals,
pubmed-meshheading:7562510-Avoidance Learning,
pubmed-meshheading:7562510-Cognition,
pubmed-meshheading:7562510-Cognition Disorders,
pubmed-meshheading:7562510-Flavobacterium,
pubmed-meshheading:7562510-Frontal Lobe,
pubmed-meshheading:7562510-Hippocampus,
pubmed-meshheading:7562510-Hydrolysis,
pubmed-meshheading:7562510-Male,
pubmed-meshheading:7562510-Microdialysis,
pubmed-meshheading:7562510-Neuropeptides,
pubmed-meshheading:7562510-Pyrrolidines,
pubmed-meshheading:7562510-Rats,
pubmed-meshheading:7562510-Rats, Inbred F344,
pubmed-meshheading:7562510-Rats, Wistar,
pubmed-meshheading:7562510-Scopolamine Hydrobromide,
pubmed-meshheading:7562510-Serine Endopeptidases,
pubmed-meshheading:7562510-Serine Proteinase Inhibitors,
pubmed-meshheading:7562510-Substrate Specificity
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer.
|
| pubmed:affiliation |
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka.
|
| pubmed:publicationType |
Journal Article
|