EN
In the clinic, multidrug therapies become standard of modern successful therapies. However, the different pharmacodynamic profi le of the drugs creates limits of using of a mixture. The discovery of numerous endogenous components which participate in the formation, transmission, modulation and perception of pain signals offers numerous strategies for the development of new analgesic. One of them is Substance P (SP). This undecapeptide Arg-Pro-Lys-Pro-Gln-Gln-PhePhe-Gly-Leu-Met-NH2 is widely distributed throughout the central nervous system and is highly expressed on areas that are critical for the regulation of pain infl ux, affective behavior and stress. For activation of the receptor neurokinin-1 (NK-1) the C-terminal sequence of SP is essential but not all the effects of SP are mediated through the Cterminal fragment. N-terminal fragment, such as SP(1-7) induces antinociception and desensitization of several SP-induced behaviors. SP has been suggested to modulate the expression of opiate tolerance and withdrawal behaviours in rodents. This communication will present the results of creating the mixture SP and dermorphin administered together at the same time, because it is very important to describe pharmacological mechanism of these two compounds. This is the fi rst step to design new analgesics hybrids where in one molecule we have two different pharmacophores: C-terminal fragment of substance P and N- terminal fragment replaced with dermorphin. Presented studies have been supported with EU grant Normolife (LSHC-CT-2006-037733)