Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice.

Abstract

The effect of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures and progressively increasing mortality were seen at higher doses. Prior administration of CPA resulted either in a delay of seizure onset and unchanged mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the effect of CPX administration resulted in mortality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A1 receptor agonists may protect against NMDA-evoked seizures and that the adenosine A1 receptor may be directly involved in these actions.

• Authors: D K Von Lubitz, I A Paul, M Carter, K A Jacobson
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 249 Issue 3 Pg. 265-70 (Nov 16 1993) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8287913 (Publication Type: Journal Article)

Chemical References

• Xanthines
• N(6)-cyclopentyladenosine
• N-Methylaspartate
• 1,3-dipropyl-8-cyclopentylxanthine
• Adenosine

Topics

• Adenosine (administration & dosage, analogs & derivatives, pharmacology)
• Animals
• Drug Interactions
• Injections, Intraperitoneal
• Male
• Mice
• Mice, Inbred C57BL
• Motor Activity (drug effects)
• N-Methylaspartate (toxicity)
• Seizures (chemically induced, mortality, prevention & control)
• Survival Rate
• Temperature
• Xanthines (administration & dosage, pharmacology)