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 central neurotropic activity of an aqueous-alcoholic extract from Rhaponticum carthamoides (Wilid.) (Leucea carthamoides D.C.) cultivated in Bulgaria was studied in experiments on albino mice, rats and cats. In doses up to 40 g/kg the extract was non-toxic. Administered in definite doses in mice and rats, it exerted a moderate central stimulating action: increased ambulation and rearing in rats ("open field" test); increased central nervous system excitability ("jumping" test); had a slight antinarcotic effect; improved learning and memory in rats trained in a maze; and increased the physical strength of rats subjected to exhaustive swimming. Administered intraduodenally in cats the extract exerted a hypotensive effect.

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1. In vitro studies of the potential antioxidant activity of the selective cyclo-oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug amtolmetin guacyl (AMG) were carried out. The study included experiments on the ability of these drugs to affect some indices of the oxidative stress [lipid peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in rat stomach and colon mucosa and in liver. 2. Celecoxib and AMG did not change the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue preparations. An increased superoxide dismutase (SOD) activity and a tendency to a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found, but only in the presence of AMG. 3. In the liver, both celecoxib and AMG decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced only in the presence of AMG. 4. Experiments aimed at studying celecoxib and AMG in free oxygen radical-generating systems were also carried out. AMG and tolmetin (the main metabolite of AMG) inhibited OH*-provoked deoxyribose degradation in a Fenton system. Celecoxib had no effect on free radicals when tested in the same system. 5. In conclusion, the results of the present in vitro studies suggest that AMG and celecoxib possess antioxidant and metal-chelating abilities, which might contribute to their beneficial effects.