Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri

Amaç: Bu çalışmanın amacı, bazı piperazin alkanol türevi bileşiklerin olası antinosiseptif etkinliklerinin bazı nosiseptif testler ile araştırılmasıdır. Gereç ve Yöntem: Piperazin alkanol türevlerinin (20 mg/kg) mekanik, termal ve kimyasal ağrılı uyarana karşı potansiyel antinosiseptif etkileri kuyruk sıkıştırma, sıcak plaka, asetik asid kıvranma ve formalin testleri ile araştırılmıştır. Test edilen bileşiklerin farelerin motor koordinasyonları üzerine olası etkinliğini değerlendirmek üzere Rota-Rod testi yapılmıştır. Bulgular: Referans ilaç olarak kullanılan morfin kuyruk sıkıştırma, sıcak plaka, asetik asid kıvranma ve formalin testlerinde beklenen analjezik etkiyi göstermiştir. 2-(4-sübstitüepiperazin-1-il)-1-fenilpropan-1-ol türevlerinden; 2-hidroksietil (C3), fenil (C6), 4-metilfenil (C7), 4-klorofenil (C8), 4-florofenil (C9), 4-nitrofenil (C10) ve benzhidril (C11) sübstitüentlerini taşıyan bileşikler, kuyruk sıkıştırma ve sıcak plaka testlerinde mekanik ve termal ağrılı uyarana karşı farelerin reaksiyon sürelerini artırmıştır. Aynı test bileşikleri asetik asid kıvranma ve formalin testlerinde, kimyasal uyarı aracılıklı nosiseptif cevapları azaltmıştır. C7, C8 ve C11 kodlu test bileşiklerinin antinosiseptif etkileri C3, C6, C9 ve C10 kodlu test bileşiklerinden istatistiksel olarak daha anlamlı bulunmuştur. Non-selektif opioid reseptör antagonisti nalokson (5 mg/kg) tüm nosiseptif testlerde gözlenen antinosiseptif etkiyi tamamen antagonize etmiştir. Sonuç: Bu bulgular, C3, C6-C11 kodlu test bileşiklerinin antinosiseptif etkilerini ortaya koymuş ve bu etkinin hem santral hem de periferik mekanizmalar ile ilişkili olduğuna işaret etmiştir. Ayrıca, nalokson antagonizması söz konusu aktiviteye opioid mekanizmaların katılımını göstermektedir.

Anahtar Kelimeler:

Piperazin alkanol, kuyruk sıkıştırma testi, sıcak plaka testi, asetik asid kıvranma testi, formalin testi, opioid, Rota-Rod testi

The antinociceptive effects of some piperazine alkanol derivatives

Purpose: The aim of this study was to investigate probable antinociceptive activities of some piperazine alkanol derivatives in some nociceptive tests. Materials and Methods: Potential antinociceptive activities of the piperazine alkanol derivatives (20 mg/kg) 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.Results: Morphine used as a reference drug exhibited analgesic effect in tail-clip, hot-plate, acetic acid-induced writhing, and formalin tests, as expected. 2-(4-substituted-piperazin-1-yl)-1-phenylpropan-1-ol compounds, which carry 2-hydroxyethyl (C3), phenyl (C6), 4-methylphenyl (C7), 4-chlorophenyl (C8), 4-fluorophenyl (C9), 4-nitrophenyl (C10) and benzhydryl (C11) substituents, 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 the compounds C3, C6, C9, and C10. Naloxone, non-selective opioid receptor antagonist (5 mg/kg), totally antagonized the antinociceptive effect observed in all of the nociceptive tests. Conclusion: These findings revealed antinociceptive activity of the compounds C3, C6-C11, and pointed out that this effect was associated with both central and peripheral mechanisms. In addition, naloxone antagonism indicated the involvement of opioid mechanisms in the activity.

Keywords:

Piperazine alkanol, tail-clip test, hot-plate test, acetic acid-induced writhing test, formalin test, opioid, Rota-Rod test,

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