Problem:
The approach in which compounds are designed to interact with a wide spectrum of targets involved in pain signal formation and transmission is a new and original therapeutic strategy, opposite to current strategies that use drugs which are as receptor-selective as possible. The project's major goal is chemical design of new multitarget molecules and analysis of their pharmacological properties that will result in the selection of several new compounds for further clinical evaluation as a new generation of potent analgesics for multicomponent cancer pain treatment.

Aim:
The project will involve three general complementary scientific objectives: chemistry, in vitro biopharmacology and in vivo pharmacology that will be accomplished by multidisciplinary teams integrated in the project.

Synthesis of new compounds, designed by theoretical (SAR) analysis, will be synthesized in chemical laboratories. Hundred new compounds will be designed and synthesized on initial stages of the project. These compounds will be preselected in in vitro tests. The in vitro tests comprise receptor affinity evaluation and functional cell-based assays. The selected (expected 6) compounds will be finally characterized in vivo in an animal model of cancer pain.

Expected results:
The application of a new generation of medicines designed under the NORMOLIFE project will reduce side effects generated by traditional opioids in central nervous system, including tolerance, dependence, constipation, euphoria, etc. The major prospective application of the results will be a more effective treatment of acute as well as chronic, neuropathic and inflammatory cancer pain of patients with advanced stages of the disease. We predict that the project will be able also to define the differences between the spectrum of pain symptoms and pain progression in progressive cancer typical for female (ovarian) and male (prostate) patients. The establishment of such differences will help to propose different pain treatment for women and men.

Potential applications:
The experimental preclinical data of the newly-developed compounds will allow for selection and proposition of new medicines for further clinical evaluation.