A simple intravenous infusion method in rodents for determining the potency of anticonvulsants acting through GABAergic mechanisms.
A simple method of intravenous infusion of convulsant drugs (pentetrazol and bicuculline) into the tail vein of rats has been used to determine seizure threshold and construct log-dose seizure threshold response curves for several anticonvulsant drugs (diazepam, phenobarbitone, pentobarbitone, chlormethiazole and valproate). It has been shown that an index of the dose required to increase seizure threshold by 50% (TI50) can be obtained using small numbers of animals. The advantages of this method over that of the subcutaneous pentetrazol method are several: small numbers of animals required, speed and reproducibility. The data also demonstrate the concordance between TI50 values obtained using pentetrazol and bicuculline as the convulsant agent. It is suggested that this method can be used routinely in screens of anticonvulsant drugs thought to work through GABAergic mechanisms.
Green
A R
AR
Astra Neuroscience research Unit, London, UK.
Murray
T K
TK
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D007262:Infusions, Intravenous / Q000295:instrumentation*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000927:Anticonvulsants; D003292:Convulsants; D005680:gamma-Aminobutyric Acid