Antiamnesic effects of D-pipecolic acid and analogues of Pro-Leu-Gly-NH2 in rats.
The antiamnesic effects of prolyl-leucyl-glycinamide (PLG) and analogues of this tripeptide were investigated in rats. Retrograde amnesia was induced by electroconvulsive shock treatment and the degree of amnesia was characterized by the attenuation of one-trial learning passive avoidance response. PLG resulted in dose-dependent attenuation of retrograde amnesia. Structural modifications included N-terminal protection, substitution of the C-terminal NH2 group, replacement of the N-terminal amino acid, and replacement of the second amino acid of the tripeptide. Some tripeptides, all of them containing D-pipecolic acid instead of the N-terminal proline, were more effective than PLG. Therefore, D-pipecolic acid, D-pipecolamide and their N-terminally protected analogues were also investigated, and were found to have powerful antiamnesic effects.
Kovács
G L
GL
Institute of Pathophysiology, University Medical School, Szeged, Hungary.
Szabó
G
G
Telegdy
G
G
Baláspiri
L
L
Pálos
E
E
Szpornyi
L
L
D000647:Amnesia / Q000188:drug therapy*; D000648:Amnesia, Retrograde / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D010875:Pipecolic Acids; D009075:MSH Release-Inhibiting Hormone