Investigation of the antinociceptive effects of some piperazine alkanol derivatives

In this thesis study, piperazine-alkanol derivatives were synthesized and their probable antinociceptive activities were investigated in some nociceptive test models. Piperazine-alkanol compounds were synthesized as a result of reduction of 1-phenyl-2-(4-substitutedpiperazin-1-yl)propanone derivatives with sodium borohydride. Chemical structures of synthesized compounds were elucidated by 1H-NMR and Elementary analysis data. Potential antinociceptive activities of the synthesized compounds against mechanic, thermal and chemical nociceptive stimuli were evaluated by tail-clip, hot-plate, acetic acid-induced writhing, and formalin tests. Rota-rod test was performed to evaluate probable effect of the test compounds on motor coordination of mice. Morphine used as a reference drug exhibited analgesic effect in tail-clip, hot-plate, acetic acid-induced writhing, and formalin tests, as expected. C3, C6, C7, C8, C9, C10, and C11 coded test compounds applied at 20 mg.kg-1 dose, increased the reaction time of mice against mechanic and thermal nociceptive stimuli in tail-clip and hot-plate tests, respectively. The same test compounds decreased chemical stimulus induced nociceptive response in acetic acid-induced writhing and formalin tests. Antinociceptive effects of the compounds C7, C8, and C11 were found to be statistically more significant than C3, C6, C9, and C10 in analgesia tests. Naloxone, non-selective opioid receptor antagonist, at 5 mg.kg-1 dose, totally antagonized the antinociceptive effect observed in all of the nociceptive tests. Results of the Rota-Rod test revealed that antinociceptive effect was not associated with any impairment of motor coordination in animals. The findings of this study exhibited the antinociceptive activities of the C3, C6, C7, C8, C9, C10 and C11 coded test compounds and pointed out the participation of both central and peripheral mechanisms in this effect. In addition, naloxone antagonism indicated the involvement of opioid mechanisms in the activity. Findings of this study, supported the results of previous papers reporting the antinociceptive activity of various piperazine-alkanol derivatives.