Effects of nifedipine, verapamil, diltiazem and trifluoperazine on the antinociceptive activity of acetaminophen

The influence of the calcium channel blockers (CCBs) nifedipine, verapamil and diltiazem, and the calmodulin antagonist trifluoperazine on the antinoc iceptive activity of acetaminophen was studied in male albino mice. The noc iceptive response was determined by the acetic acid writhing test. Nifedipi ne (50 or 20 mg/kg), verapamil (20 mg/kg), diltiazem (70 mg/kg) and trifluo perazine (3 mg/kg) were administered orally alone or 1 h before acetaminoph en (100 mg/kg). Nifedipine (50 mg/kg), verapamil, diltiazem and trifluopera zine applied 1 h before acetaminophen potentiated its antinociceptive activ ity, which was strongest in mice injected with verapamil and nifedipine (20 mg/kg). It was established that 1 h after nifedipine (50 mg/kg) treatment, cytochrome P450 content, NADPH cytochrome c reductase and ethylmorphine-N- demethylase (EMND) activities were increased in the liver microsomes. Verap amil, diltiazem and trifluoperazine did not change the drug metabolizing en zymes studied. It is assumed that their effect on acetaminophen analgesia i s not associated with the changes in acetaminophen oxidative metabolism in the liver. (C) 2000 Prous Science. All rights reserved.