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.
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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)
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Chemical References |
- Xanthines
- N(6)-cyclopentyladenosine
- N-Methylaspartate
- 1,3-dipropyl-8-cyclopentylxanthine
- Adenosine
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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)
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