Isobolographic analysis of the interaction of tramadol with anticonvulsant drugs in mice

Abstract

Experimental research followed by clinical studies have demonstrated the existence of several types of pain, thus the pain classification according to the mediation has widely extended. In addition, the study of the interactions with pharmacodynamic mechanism expanded very much during the last years; therefore in the new theories appear significant changes concerning synergism, addition and subadditivity in binary combinations. The investigations in this paper were aimed the demonstration of the antinociceptive of some drugs with anticonvulsant action and the analysis of their binary combinations with tramadol, using isobolar analysis. As model of nociception has been used the test of abdominal constrictive response in mouse induced by Zymosan A. the test substances were administered orally alone or in fixed proportion combinations. The data obtained were subjected to isobolar analysis. According to the statistical analysis the following have been observed: the binary combination tramadol-VA has proven to be synergistic (Zmix < Zadd, f = 0,5, p1 = 677, Tc =3.936, Tt = 3,529, c = 12.78, Ft = 4.46, p < 0.05), while the binary combination tramadol-CBZ has proven to be borderline additive (Z mix < Zadd).