Suppression of audiogenic seizures in DBA/2 mice by two new dipeptide NMDA receptor antagonists.

Abstract

Two new phosphonate dipeptides, gamma-D- glutamylaminomethylphosphonate (Glu-Amp) and beta-D- aspartylaminomethylphosphonate (Asp-Amp), that are antagonists of excitation due to N-methyl-D-aspartate have been compared with omega-phosphonic-alpha-carboxylic amino acids as anticonvulsant agents in mice with sound-induced seizures. Compounds were injected intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) into DBA/2 mice 45 min prior to sound exposure, and ED50 values for suppression of the different phases of the seizure response were estimated. With i.c.v. injection Glu-Amp is 0.4-0.8 times as potent an anticonvulsant as (+/-)2-amino-7- phosphonoheptanoate and Asp-Amp is 1.3-2.5 times as potent. With i.p. injection Glu-Amp is 0.15-0.28 and Asp-Amp 0.23-0.58 times as potent as (+/-)2-amino-7-phosphonoheptanoic acid. These findings correspond to their known potency as N-methyl-D-aspartate antagonists, and are consistent with an anticonvulsant effect arising from action at a receptor sensitive to N-methyl-D-aspartate.

• Authors: A W Jones, M J Croucher, B S Meldrum, J C Watkins
• Journal: Neuroscience letters (Neurosci Lett) Vol. 45 Issue 2 Pg. 157-61 (Mar 23 1984) ISSN: 0304-3940 [Print] Ireland
• PMID: 6145126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Anticonvulsants
• Dipeptides
• Glutamates
• Glutamine
• Aspartic Acid
• 2-Amino-5-phosphonovalerate
• gamma-D-glutamylaminomethylphosphonic acid
• beta-D-aspartylaminomethylphosphonic acid
• Valine
• 2-amino-7-phosphonoheptanoic acid

Topics

• 2-Amino-5-phosphonovalerate
• Acoustic Stimulation
• Amino Acids (pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Aspartic Acid (analogs & derivatives, pharmacology)
• Dipeptides (pharmacology)
• Dose-Response Relationship, Drug
• Glutamates (pharmacology)
• Glutamine (analogs & derivatives)
• Mice
• Mice, Inbred DBA
• Seizures (drug therapy)
• Valine (analogs & derivatives, pharmacology)