Possibilities to potentiate effect of non-opioid analgesics

The aim of the present Thesis was to investigate the possibility of the improvement of analgesic efficacy of novel non-opioid analgesics selectively or preferentially inhibiting COX-2, coxibs and meloxicam, by combinations with other substancies. These analgesics have favourable profile of gastrointestinal tolerability. For this purpose, a few different approaches were used. Based on the published data, two members of the cyclooxygenase-2 inhibitors group were selected, etoricoxib and celecoxib, and their interactions with the weak opioid codeine were assayed. Analgesic efficacy of the individual drugs and their combinations was evaluated using the preclinical model of acute visceral pain (the writhing test), in mice, and the statistical method of isobolographic analysis was used to investigate the manner of interactions. Subsequently, the interactions of paracetamol and ibuprofen with codeine were also assayed using the same methods. The interaction between celecoxib and codeine was found to be additive, while that between etoricoxib and codeine was sub-additive. On the other hand, the interactions of paracetamol and ibuprofen with codeine were synergistic. In the second part of the Thesis, the potential improvement of the pharmacological properties of meloxicam was evaluated after its complexation with..