Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia.

Abstract

Intramuscular injection of selective NMDA receptor antagonists memantine and arcaine 4-fold decreased the incidence of pentylenetetrazole-induced generalized tonic-clonic seizures in rats, while the incidence of clonic seizures decreased by 1.2-1.3 times. Memantine and arcaine are characterized by low therapeutic index, i.e. induced ataxia in rats in doses exceeding the effective anticonvulsant dose by only 3.5-10 times. Intramuscular injection of IEM-1913 (combined blockade of NMDA and AMPA receptors in the brain) decreased the incidence of pentylenetetrazole-induced clonic and tonic-clonic seizures in rats by 4-8 times. The therapeutic index of IEM-1913 surpassed that of memantine and arcaine by 200-600 times.

• Authors: V E Gmiro, S E Serdyuk
• Journal: Bulletin of experimental biology and medicine (Bull Exp Biol Med) Vol. 145 Issue 6 Pg. 728-30 (Jun 2008) ISSN: 0007-4888 [Print] United States
• PMID: 19110562 (Publication Type: Journal Article)

Chemical References

• Biguanides
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• arcaine
• Memantine
• Pentylenetetrazole

Topics

• Animals
• Ataxia (chemically induced)
• Biguanides (pharmacology, therapeutic use)
• Drug Synergism
• Drug Therapy, Combination
• Epilepsy, Tonic-Clonic (chemically induced, complications, prevention & control)
• Male
• Memantine (pharmacology, therapeutic use)
• Pentylenetetrazole
• Rats
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Seizures (chemically induced, complications, prevention & control)