S 17092: a prolyl endopeptidase inhibitor as a potential therapeutic drug for memory impairment. Preclinical and clinical studies.
CNS Drug Rev
; 8(1): 31-52, 2002.
Article
en En
| MEDLINE
| ID: mdl-12070525
ABSTRACT
Any treatment that could positively modulate central neuropeptides levels would provide a promising therapeutic approach to the treatment of cognitive deficits associated with aging and/or neurodegenerative diseases. Therefore, based on the activity in rodents, S 17092 (2S,3aS,7aS)-1][(R,R)-2-phenylcyclopropyl]carbonyl]-2-[(thiazolidin-3-yl)carbonyl]octahydro-1H-indole) has been selected as a potent inhibitor of cerebral prolyl-endopeptidase (PEP). By retarding the degradation of neuroactive peptides, S 17092 was successfully used in a variety of memory tasks. These tasks explored short-term, long-term, reference and working memory in aged mice, as well as in rodents and monkeys with chemically induced amnesia or spontaneous memory deficits. S 17092 has also been safely administered to humans, and showed a clear peripheral expression of its mechanism of action through its inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects, as evidenced by EEG recording in healthy volunteers, and could improve a delayed verbal memory task. Collectively, the preclinical and clinical effects of S 17092 have suggested a promising role for this compound as an agent for the treatment of cognitive disorders associated with cerebral aging.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazoles
/
Serina Endopeptidasas
/
Inhibidores de Serina Proteinasa
/
Trastornos del Conocimiento
/
Indoles
/
Trastornos de la Memoria
Límite:
Animals
/
Humans
Idioma:
En
Revista:
CNS Drug Rev
Asunto de la revista:
FARMACOLOGIA
/
NEUROLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Francia