Nitric oxide synthase inhibitor 7-nitroindazole attenuates the behaviouralsigns of ethanol withdrawal due to pharmacokinetic interaction

We have studied the effects of a nitric oxide synthase (NOS) inhibitor, 7-n itroindazole (7-NI), on the behavioural signs of ethanol withdrawal and eth anol pharmacokinetics in mice after chronic ethanol administration. Male al bino mice received ethanol by inhalation for 18 days. Vehicle, diazepam (5. 0 mg/kg) or 7-NI (20.0 mg/kg) were administered intraperitoneally immediate ly or 6.5 h after the end of ethanol exposure. The behavioural signs of eth anol withdrawal and ethanol concentrations in blood were measured 6.5 and 7 .5 h after withdrawal. Parallel to a rapid decrease in blood ethanol concen tration the vehicle-treated mice showed behavioural signs of ethanol withdr awal severe tremor and clonic convulsions. Diazepam blocked the development of these signs and eliminated them when administered during withdrawal. 7- NI attenuated the signs of ethanol withdrawal and slowed ethanol clearance when administered immediately after the end of ethanol exposure, but had no effect when administered during withdrawal. The effect of 7-NI on ethanol withdrawal syndrome is explained by slowed ethanol clearance. Med Sci Res 2 6:821-822. (C) 1998 Lippincott Williams & Wilkins.