Dipeptides--analogues of N-acetylaspartylglutamate inhibit convulsive effects of excitatory amino acids in mice.
The effects of three dipeptide analogues of N-acetylaspartylglutamate on seizures elicited by intracerebroventricular (i.c.v.) injection of L-glutamate (GLU), N-methyl-D-aspartate (NMDA), kainate (KA) and intraperitoneal (i.p.) injection of pentylentetrazol (PTZ) were studied in mice. N-Ac-L-Phe-L-Glu was active against myoclonic seizures induced by GLU and NMDA under simultaneous i.c.v. injection. All dipeptides were ineffective against KA and PTZ convulsions. The anticonvulsant activity and potency of N-Ac-L-Phe-L-Glu were similar to that of gamma-D-glutamylglycine (gamma-DGG) for excitatory amino acids (EAA) induced seizures. These results indicate EAA antagonistic activity among dipeptides which have L-glutamic acid on C-terminal and acetylated N-terminal.
Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences, Leningrad, U.S.S.R.
L B
LB
Piotrovsky
A P
AP
Garyaev
L N
LN
Poznyakova
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology*; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000633:toxicity; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D013329:Structure-Activity Relationship
D004151:Dipeptides; D005971:Glutamates; D009498:Neurotoxins; C027172:isospaglumic acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007608:Kainic Acid; D010433:Pentylenetetrazole