Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice.
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.
Von Lubitz
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DK
Laboratory of Bioorganic Chemistry, NIH/NIDDK, Bethesda, MD 20892.
Paul
I A
IA
Carter
M
M
Jacobson
K A
KA
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate; D013696:Temperature; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*
D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; D016202:N-Methylaspartate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine