H. Păunescu 1, Oana Andreia Coman 1, L. Coman 2, F. Drăghia 3, Cristina Muşa 4, Isabel Ghiţă 1, I. Fulga 1
1 Department of Pharmacology and Pharmacotherapy, “Carol Davila” University of Medicine and Pharmacy, Bucharest
2 Department of Physiology, “Carol Davila” University of Medicine and Pharmacy, Bucharest
3 Department of Anatomy, “Carol Davila” University of Medicine and Pharmacy, Bucharest MD
Abstract
Introduction. Paracetamol has been known as analgesic for over 100 years and has a mechanism of action that still remained not elucidated until now. There are authors who state a possible cannabinoid component of the analgesic effect of paracetamol administered in high doses. Background. This work has tried to study a possible cannabinoid component of the analgesic effect of orally administered paracetamol in the writhing test with acetic acid 0.75% v/v, 0.15 ml/10 g body weight, by using AM281 as a cannabinoid receptor antagonist. Materials and methods. In two experiments, 24 respectively 40 mice, separated in 4 groups each, have been used. In the first experiment 3 doses of paracetamol in geometric progression have been used to determine the ED50 (Effective Dose 50). In the second experiment 600 mg/kg (approximated as ED80) of paracetamol, AM 281 1mg/kg body weight, or combinations of both have been used. Paracetamol or vehicle have been administered 1 hour before testing, AM281 or vehicle 30 minutes before testing and the writhes have been observed over a 5 minutes period. The statistical analysis has required the use of ANOVA and of post hoc multiple comparison tests. Microsoft Excel and SPSS 15 programs have been used. Results. Statistically significant analgesia has been obtained for groups treated with paracetamol 300 and 600 mg/kg respectively in the first experiment. The ED50 was 301 mg/ kg. No effect has been obtained for the AM281, and the AM281 has not antagonized the analgesic effect of paracetamol administered in a dose of 600 mg/kg body weight in the second experiment. Discussion and conclusions. There has been a dose-effect relationship for paracetamol in the writhing test. AM281 has had no effect per se and has not influenced the effect of paracetamol administered in a 600 mg/kg dose. The blockade of the cannabinoid receptors under our experimental conditions has not produced any effect. Paracetamol in moderate doses (600 mg/kg) did not seem to interfere with the metabolism of the endogenous cannabinoids to such an extent as to produce an analgesic effect through this mechanism. Our results might be due to the fact that AM 404, a compound derived from paracetamol and arachidonic acid, which is supposed to interfere with the cannabinoid system, did not accumulate at the moderate doses of paracetamol used in the present experiment.