Diazepam reverses the effects of pentylenetetrazole in rat pups by acting at type 2 benzodiazepine receptors.
Pentylenetetrazole (75 mg/kg) induced a characteristic coarse body tremor (accompanied by limb extension) and hyperactivity in 4-day-old rat pups. These effects were reversed by diazepam (0.5 and 2 mg/kg) but not by CL 218,872 (10 and 20 mg/kg) which is selective for type 1 benzodiazepine receptors. Diazepam did not affect the brain concentrations of pentylenetrazole, indicating that the reversal was not based on a pharmacokinetic interaction. Neither diazepam nor CL 218,872 had significant effects on the behavior of the rat pups, although diazepam (2 mg/kg) tended to increase locomotor activity. The results suggest that diazepam displays an anticonvulsant effect in the neonatal rat which is mediated by type 2 receptors.
Johnston
A L
AL
MRC Neuropharmacology Research Group, School of Pharmacy, University of London.
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S E
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Dingemanse
J
J
Aranko
K
K
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D010433:Pentylenetetrazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014202:Tremor / Q000139:chemically induced*
D000927:Anticonvulsants; D011963:Receptors, GABA-A; D003975:Diazepam; D010433:Pentylenetetrazole