Investigation of the possible antinociceptive effects of newpirazoline derivatives

Pyrazoline is a five-membered heterocyclic ring containing two adjacent nitrogen atoms. In this thesis study, 12 original pyrazoline derivatives (3a-3l) were synthesized and the possible antinociceptive effects of these compounds were investigated. The chemical structure was elucidated using 1 H-NMR and 13 C-NMR spectroscopy methods. The effects of the synthesized compounds on the motor activities of mice were examined using the activity meter test; and the potential antinociceptive effects against thermal, mechanical and chemical painful stimuli were evaluated using hot plate, tail immersion, tail clip, and acetic acid writhing tests. None of the molecules in the series in the study caused a significant change in the motor performance of mice. The test compounds coded 3i-3l, administered at a dose of 100 mg/kg, increased the reaction times of the mice to thermal and mechanical painful stimuli in the hot plate and tail clip tests. This indicated that the substances exerted their effects via the supraspinal and spinal pathways, respectively. The compounds coded 3h, 3j, 3l showed antinociceptive activity mediated by spinal mechanisms in the tail immersion test, in which thermal painful stimulus was applied. In the acetic acid test where peripheral analgesia was evaluated, it was observed that all compounds (3a-3l) reduced the number of writhings in the experimental animals. These findings supported the results of previous studies indicating the antinociceptive activity potential of pyrazoline derivative test compounds. However, in order to become drug candidates, the mechanism of centrally and peripherally mediated effects of these pyrazoline compounds should be investigated with various in vivo and in silico methods. Keywords: Pyrazoline, Antinociceptive, Hot plate test, Tail immersion test, Tail clip test, Acetic acid induced writhing test