THE EFFECTS OF THE NITRIC OXIDE SYNTHASE INHIBITOR 7-NITROINDAZOLE ON ETHANOL PHARMACOKINETICS IN RATS AFTER ACUTE AND CHRONIC ETHANOL ADMINISTRATION

The aim of this work was to study the effects of the nitricoxide synthase (NOS) inhibitors 7-n,troindazole (7-NI) and N^G-nitro-L-arginine(L-NOARG) on the effects and pharmacokinetics of ethanol inrats. Ethanol at a dose of 4 g/kg, i.p. induced sleep in rats(sleep time: 117.2 ± 30.7 min). Administration of theNOS inhibitors 7-NI (20 mg/kg, i.p.) and L-NOARG (20 mg/kg,i.p.) 30 min before ethanol significantly increased the durationof ethanol-induced sleep. L-NOARG also significantly increasedthe toxicity of ethanol as evidenced by increased post-experimentallethality Ethanol at a dose of 2 g/kg (i.p.) did not inducesleep in vehicle-treated rats; however, the combined administrationof ethanol (2 g/kg) and 7-NI at doses of 40, 80, and 120 mg/kgcaused sleep, for 49.4 ± 3.7, 204.0 ± 13.3, and447.5 ± 62.8 min, respectively. L-NOARG (20 mg/kg) hadno effect on ethanol concentrations in blood after acute ethanoladministration (4 g/kg). 7-NI in lower doses (20 and 40 mg/kg)had no effect and in higher doses (80 and 120 mg/kg) significantlyslowed ethanol clearance during the 12 h after ethanol administration.The effect of 7-NI (20 mg/kg) on ethanol pharmacokinetics afterchronic ethanol administration (inhalation for 18 days) wasalso studied. The administration of 7-NI immediately after theend of ethanol exposure had a pronounced effect on ethanol pharmacokinetics;in 7-NI-treated rats the fall in ethanol concentrations wassignificantly slower as compared with vehicle-treated rats.In 7-NI- treated rats, blood-ethanol levels were higher at 3,6, 9, and 12 h after the end of ethanol exposure.