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© 1998 Medical Council on Alcohol

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

V. VASSILJEV, A. KALDA, P. POKK1,*, M. VÄLI and A. ZHARKOVSKY1

Department of Pathologic Anatomy and Forensic Medicine Estonia
1Department of Pharmacology, Faculty of Medicine, University of Tartu Ülikooli Str. 18, EE 2400 Tartu, Estonia

*Author to whom correspondence should be addressed

Received 3 March 1998; first review notified 18 May 1998; accepted 16 June 1998

The aim of this work was to study the effects of the nitric oxide synthase (NOS) inhibitors 7-n,troindazole (7-NI) and NG-nitro-L-arginine (L-NOARG) on the effects and pharmacokinetics of ethanol in rats. Ethanol at a dose of 4 g/kg, i.p. induced sleep in rats (sleep time: 117.2 ± 30.7 min). Administration of the NOS inhibitors 7-NI (20 mg/kg, i.p.) and L-NOARG (20 mg/kg, i.p.) 30 min before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG also significantly increased the toxicity of ethanol as evidenced by increased post-experimental lethality Ethanol at a dose of 2 g/kg (i.p.) did not induce sleep in vehicle-treated rats; however, the combined administration of ethanol (2 g/kg) and 7-NI at doses of 40, 80, and 120 mg/kg caused sleep, for 49.4 ± 3.7, 204.0 ± 13.3, and 447.5 ± 62.8 min, respectively. L-NOARG (20 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (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) significantly slowed ethanol clearance during the 12 h after ethanol administration. The effect of 7-NI (20 mg/kg) on ethanol pharmacokinetics after chronic ethanol administration (inhalation for 18 days) was also studied. The administration of 7-NI immediately after the end of ethanol exposure had a pronounced effect on ethanol pharmacokinetics; in 7-NI-treated rats the fall in ethanol concentrations was significantly 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.


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P. Pokk, E. Sepp, V. Vassiljev, and M. Vali
The effects of the nitric oxide synthase inhibitor 7-nitroindazole on the behaviour of mice after chronic ethanol administration
Alcohol Alcohol., May 1, 2001; 36(3): 193 - 198.
[Abstract] [Full Text] [PDF]


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