DEVELOPMENT OF COMPLEX PHARMACOTHERAPY OF SEVERE AND MODERATE PAIN. PART I. MULTITARGETED COMBINATION OF OPIOIDS AND NON-OPIOID ANALGESICS WITH CENTRAL EFFECTS

Medicines based on opioid analgesics are the basic means of pharmacotherapy of severe pain at present. Approaches to increase efficacy and safety of complex opioid analgesia are described and classified based on analysis of medicinal and veterinary analgesics acting on different CNS biotargets. Principles of creation multitargeted fixed-dose combinations (FDC) and some schemes of multimodal analgesia are demonstrated by the example of opioid combinations with ligands of alpha-2 adrenergic receptors, antagonists of excitatory amino acid receptors, GABA ligands, their derivatives and analogues, cannabinoids, monoamines reuptake inhibitors and opiate receptor antagonists. Importance of multitargeted substances in general including codrug approach for facilitating of drug delivery and bioactivity enhancement were demonstrated. Development of opioid formulations with low level of dependency and tolerance and also principles to protect opioid formulations against non-medical use were described. Methodology of multitargeted analgesia is one of the drivers in drug development on the background of low progress in the development of new effective molecules for relief of severe and moderate pain. The greatest interest is development of FDC with drug potentiation and efficacy at low doses. It allows creating wide variety of analgesics formulations