EVALUATING THE SYNERGISM BETWEEN SILDENAFIL AND METFORMIN IN AN ANIMAL MODEL OF DIABETIC NEUROPATHY INDUCED BY ALLOXAN

Abstract

Given the complex mechanism of diabetic neuropathy, evaluating the effect of drug combinations in this pathology is of an utmost importance. The aim of this study was to evaluate the synergism between sildenafil and metformin in an alloxan induced diabetic neuropathy mouse model. The pain latency times obtained for male mice in the cold and heat hypersensitivity tests, as well as the administered drug doses were processed and analysed in Python Programming Language by using the Multi-dimensional Synergy of Combinations algorithm, with the computation of three drug synergy indicator types, based on efficacy, potency and cooperativity. The results showed mixed values in terms of the synergism and antagonism between sildenafil and metformin on neuropathic pain, but drug synergy was identified for at least one indicator for all experimental tests. While this study is the first to evaluate the synergism between sildenafil and metformin on diabetic neuropathy, future studies must aim in analysing a higher number of drug doses, with the development of a model which might be translated to clinical data.