The aim of the present study was the synthesis and the biological screening of new analogs of Ac-RYYRWK-NH2, modified at the N-terminal with 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids. The four newly synthesized ligands for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) have been prepared by solid-phase peptide synthesis--Fmoc-strategy. These compounds were tested for agonistic activity in vitro on electrically stimulated smooth-muscle preparations isolated from vas deferens of Wistar rats. Our data showed that substitution of Arg at position 1 with aminophosphonates moiety decreased significantly the affinity of ligands to the NOP receptor. Furthermore, the enlargement of the cycle (with 5-8 carbon atoms) additionally diminished both the activity and the selectivity for NOP-receptor.

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.

The present study aimed to investigate the effects of pentoxifylline (PTX) on the carrageenan (CG)-induced paw oedema and on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver, 4 and 24 h after CG injection. PTX (50 mg kg(-1) , i.p.), administered 30 min before CG, decreased the paw oedema, 2-4 h after CG administration. The drug protected CG-induced decrease of glutathione (non-enzyme antioxidant) and had no effect on CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of GSH-conjugated antioxidant enzymes). The drug showed a good antioxidant capacity in chemical systems, generating reactive oxygen species. The present results suggest that the antioxidant activity of PTX might contribute to its beneficial effects in liver injuries.