Chronic pain is a health problem with high prevalence and an enormous negative impact on affected individuals and society. Pharmacological options for treating this pathology are limited and are often associated with a number of serious side effects, so finding new therapeutic agents to reduce the unnecessary and unacceptable burden of chronic pain is essential.
This project focuses on the identification of novel, highly effective analgesics among molecules already used therapeutically for other indications. This strategy, known as drug repositioning, has become popular in pharmaceutical research in recent years because it is cost-effective, requires little time, and the associated risks are minimal. Thus, productivity problems are solved by reducing the time required for drug development. By already knowing the pharmaco-toxicological properties of the substances involved, the risk of failure due to the occurrence of adverse reactions is minimized.
The new repositioned analgesics will act by enhancing endogenous cannabinoid transmission, more specifically by inhibiting the main enzymes that degrade endocannabinoids: monoacylglycerol lipase and fatty acid amide hydrolase. Increasing the level of endocannabinoids will cause activation of CB1 and CB2 receptors, leading to intense analgesic and anti-inflammatory effects.
In silico methods (analysis of structure-activity relationships, data mining and molecular docking studies) will be used to identify possible inhibitors of the above-mentioned enzymes. The in silico results will be further confirmed by in vitro studies (evaluation of enzyme inhibition by IC50 determination) and in vivo studies (evaluation of the analgesic effect in rodent models of diabetic neuropathy and Freund's induced rheumatic arthritis), in order to obtain effective analgesics in treatment of chronic pain