New N-(dimethylamino)ethyl derivatives of phthalazinones and pyridopyridazinones 7, 9 were synthesized and assayed as potential analgesic agents in the hot-plate, tail-flick, and writhing tests. Pharmacological assay demonstrated that eight (in ten) of the newly synthesized compounds showed antinociceptive activity. Especially, 2-[2-(dimethylamino)ethyl]-4-phenyl-2H-phthalazin-1-one 7a showed remarkably higher antinociceptive activity in all tests. This is connected with influence on supraspinal, spinal, and peripheral structures. The decreased sensitivity to the pain stimulus in the hot-plate was higher than that of metamizole.

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The aim of this study was to establish the effect of naturally occurring antioxidant -carnosine -on the doxorubicin induced cardiotoxicity in a rabbit model. For this purpose we evaluated the influence of doxorubicin administration alone and in a combined therapy with carnosine on the haemodynamic parameters and on the degree of cardiac muscle cells alterations in rabbits. The rabbits were divided into four groups. One group of rabbits was injccted with doxorubicin in a dose of 2 mg kg -1 weekly for 7 weeks to induce congestive heart failure. Another group of rabbits received the same doses of doxorubicin simultaneously with carnosine in a dose of 100 mg kg 1 p.o. daily for 9 weeks. Administration of carnosine was started 1 week prior to the first dose of doxorubicin and was ended one week after the administration of the last dose of doxorubicin. The control groups of animals received 0.9% NaCl and carnosine alone. The following haemodynamic parameters were estimated: heart rate, mean arterial pressure, cardiac index, stroke index and total peripheral resistance. Registration of the haemodynamic parameters in rabbits was performed by Doppler method. Carnosine normalised the values of mean arterial pressure in rabbits receiving doxorubicin, and increased the values of cardiac index and stroke index. The influence of carnosine on total peripheral resistance was not statistically significant, but there was a decreasing tendency. The degree of cardiac muscle cell alterations was examined by light microscopy using Mean Total Score technique. The histopathological studies revealed smaller damage of cardiac muscle in rabbits which received doxorubicin and carnosine, in comparison to animals receiving doxorubicin alone. Carnosine seems to be car dioprotective during doxorubicin administration.