Synergistic action of pyrazole on ethanol incoordination: differential metabolic and central nervous system effects

The influence of pyrazole on ethanol-induced incoordination was measured by a modified tilting-plane technique. Pyrazole (1–77 mmol/kg; 120 mg/kg) and/or ethanol (32.6 mmol/kg; 1.5 g/kg) was given intraperitoneally to rats. Impairment of coordination was related to blood ethanol concentrations. The mean maximal impairment was significant in all conditions. For ethanol alone the maximal impairment was 8.7%, for pyrazole alone 4.8% and for ethanol + pyrazole 16.5 %. Ethanol alone induced a total impairment, assessed planimetrically, of 530 units. Pyrazole alone induced an impairment gradually increasing with time (totally 1070 units). When pyrazole was combined with ethanol, the rate of ethanol elimination was reduced by 81%, and the time it remained in the blood was prolonged from 196 ± 11 to 850 ± 16 min. The rate of disappearance was reduced from 8.05 to 1.57 μg/ml per min. The total impairment increased to 5600 units, indicating a synergistic interaction between ethanol and pyrazole, which is contrary to the normalizing effects of pyrazole on ethanol-induced metabolic changes. A “post-drug” impairment was observed one week after pyrazole, while no such effects were found after repeated administration of saline or ethanol alone in control animals. Thus, pyrazole showed acute and long-term toxic eifects.