ABSTRACT
The effects of some dipeptides, analogues of N-acetyl-alpha-L-aspartyl-L-glutamate, were studied after i.c.v. administration into mice in acute experiments. N-Acetyl-alpha-L-aspartyl-L-glutamate itself did not induce seizures in animals, but prevented glutamate-induced convulsions. All other dipeptides possessed excitatory glutamate-like actions. Some structural requirements for the excitatory effects of the dipeptides are discussed.
Subject(s)
Dipeptides/pharmacology , Seizures/chemically induced , Animals , Anticonvulsants/pharmacology , Convulsants , Dipeptides/administration & dosage , Dipeptides/chemistry , Glutamates/pharmacology , Injections, Intraventricular , Mice , Receptors, Amino Acid , Receptors, Cell Surface/drug effects , Receptors, Cell Surface/physiology , Seizures/prevention & control , Structure-Activity RelationshipABSTRACT
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.
