Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri

DEMİR, Ümide Özkay; AKAN, Bürge Doğruer

doi:10.17826/cumj.490690

Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri

Bürge Doğruer Akan, (Anadolu Üniversitesi, Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, Eskişehir, Türkiye)

Ümide Özkay DEMİR (Anadolu Üniversitesi, Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, Eskişehir, Türkiye)

Cukurova Medical Journal

3 0

Yıl: 2019 Cilt: 44 Sayı: 3 Sayfa Aralığı: 729 - 744 Metin Dili: Türkçe DOI: 10.17826/cumj.490690 İndeks Tarihi: 01-12-2020

Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri

Öz:

Amaç: Bu çalışmanın amacı, bazı piperazin alkanol türevibileşiklerin olası antinosiseptif etkinliklerinin bazınosiseptif testler ile araştırılmasıdır.Gereç ve Yöntem: Piperazin alkanol türevlerinin (20mg/kg) mekanik, termal ve kimyasal ağrılı uyarana karşıpotansiyel antinosiseptif etkileri kuyruk sıkıştırma, sıcakplaka, asetik asid kıvranma ve formalin testleri ilearaştırılmıştır. Test edilen bileşiklerin farelerin motorkoordinasyonları üzerine olası etkinliğini değerlendirmeküzere Rota-Rod testi yapılmıştır.Bulgular: Referans ilaç olarak kullanılan morfin kuyruksıkıştırma, sıcak plaka, asetik asid kıvranma ve formalintestlerinde 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) vebenzhidril (C11) sübstitüentlerini taşıyan bileşikler, kuyruksıkıştırma ve sıcak plaka testlerinde mekanik ve termalağrılı uyarana karşı farelerin reaksiyon sürelerini artırmıştır.Aynı test bileşikleri asetik asid kıvranma ve formalintestlerinde, kimyasal uyarı aracılıklı nosiseptif cevaplarıazaltmıştır. C7, C8 ve C11 kodlu test bileşiklerininantinosiseptif etkileri C3, C6, C9 ve C10 kodlu testbileşiklerinden istatistiksel olarak daha anlamlıbulunmuştur. Non-selektif opioid reseptör antagonistinalokson (5 mg/kg) tüm nosiseptif testlerde gözlenenantinosiseptif etkiyi tamamen antagonize etmiştir.Sonuç: Bu bulgular, C3, C6-C11 kodlu test bileşiklerininantinosiseptif etkilerini ortaya koymuş ve bu etkinin hemsantral hem de periferik mekanizmalar ile ilişkili olduğunaişaret etmiştir. Ayrıca, nalokson antagonizması söz konusuaktiviteye opioid mekanizmaların katılımınıgöstermektedir.

Anahtar Kelime:

Konular: Astronomi ve Astrofizik Farmakoloji ve Eczacılık

The antinociceptive effects of some piperazine alkanol derivatives

Öz:

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 acidinduced 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-substitutedpiperazin-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.

Anahtar Kelime:

Konular: Astronomi ve Astrofizik Farmakoloji ve Eczacılık

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Nguelefack TB, Dutra RC, Paszcuk AF, Andrade EL, Tapondjou LA, Calixto JB. Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NOcGMP-ATP-sensitive-K(+) channel activation. J Ethnopharmacol. 2010;128:567-74.
2. Buschmann H, Christoph T, Friderichs E, Maul C, Sundermann B (editors). Analgesics: From chemistry and pharmacology to clinical application. 1st ed., Germany: Weinheim: Wiley-VCH. 2002;1-264.
3. Jagerovic N, Cano C, Elguero J, Goya P, Callado LF, Meana JJ et al. Long-acting fentanyl analogues: synthesis and pharmacology of N-(1- phenylpyrazolyl)-N-(1-phenylalkyl-4- piperidyl)propanamides. Bioorg Med Chem. 2002;10:817-27.
4. Xiong Y, Zhao X, Sun Q, Li R, Li C, Ye J. Antinociceptive mechanism of the spirocyclopiperazinium compound LXM-10 in mice and rats. Pharmacol Biochem Behav. 2010;95:192-7.
5. Moore ND. In search of an ideal analgesic for common acute pain. Acute Pain. 2009;11:129-37.
6. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56:387-437.
7. Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N et al. Opioid complications and side effects. Pain Physician. 2008;11:105-20.
8. Shaquiquzzaman M, Verma G, Marella A, Akhter M, Akhtar W, Khan MF et al. Piperazine scaffold: A remarkable tool in generation of diverse pharmacological agents. Eur J Med Chem. 2015;102:487-529.
9. Nozaki M, Niwa M, Imai E, Hori M, Fujimura H. (1,2- Diphenylethyl) piperazines as potent opiate-like analgesics; the unusual relationships between stereoselectivity and affinity to opioid receptor. Life Sci. 1983;33:431-4.
10. Nikolova M, Fajad K, Natova L. Synthesis and pharmacological screening of a group of piperazine derivatives. Analgesic activity. Farmaco. 1993;48:459- 72.
11. Abdel-Salam OM, El-Batran S. Pharmacological investigation of trimetazidine in models of inflammation, pain and gastric injury in rodents. Pharmacology. 2005;75:122-32.
12. Biancalani C, Giovannoni MP, Pieretti S, Cesari N, Graziano A, Vergelli C et al. Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain. J Med Chem. 2009;52:7397-409.
13. Kam YL, Rhee HK, Rhim H, Back SK, Na HS, Choo HY. Synthesis and T-type calcium channel blocking activity of novel diphenylpiperazine compounds, and evaluation of in vivo analgesic activity. Bioorg Med Chem. 2010;18:5938-44.
14. Chen Y, Wang G, Xu X, Liu BF, Li J, Zhang G. Design, synthesis and biological activity evaluation of arylpiperazine derivatives for the treatment of neuropathic pain. Molecules. 2011;16:5785-806.
15. Chae E, Yi H, Choi Y, Cho H, Lee K, Moon H. Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives as new analgesic agents. Bioorg Med Chem Lett. 2012;22:2434-9.
16. Wild KD, McCormick J, Bilsky EJ, Vanderah T, McNutt RW, Chang KJ et al. Antinociceptive actions of BW373U86 in the mouse. J Pharmacol Exp Ther. 1993;267:858-65.
17. Gengo PJ, Pettit HO, O'Neill SJ, Wei K, McNutt R, Bishop MJ, Chang KJ. DPI-3290 [(+)-3-((alpha-R)- alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N-(3-fluorophenyl)-Nmethylbenzamide]. I. A mixed opioid agonist with potent antinociceptive activity. J Pharmacol Exp Ther. 2003;307:1221-6.
18. Barn DR, Caulfield WL, Cottney J, McGurk K, Morphy JR, Rankovic Z et al. Parallel synthesis and biological activity of a new class of high affinity and selective delta-opioid ligand. Bioorg Med Chem. 2001;9:2609-24.
19. Falconner B, Pinhas H. Piperazine alkanols. U.S Patent Appl. No: 782051 (1978).
20. Li J, Wang G, Zhang G, Yang X, Xie P, Zhang L, Xu X, Wang Y. Substituted phenylpiperazinyl aralkylalcohol derivatives, Pharmaceutical compositions containing such derivatives and uses thereof. 2011;U.S Patent Appl. No:US20110294822A1.
21. Demir Özkay Ü, Yurttaş L, Özkay Y, Üçel UI, Can ÖD, Öztürk Y. Synthesis of new 1-phenyl-2-(4- substituted-piperazin-1-yl)-propanol derivatives and evaluation of their antidepressant-like effects. Arch Pharm Res. 2013;36:802-11.
22. Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci. 2001;26:30-6.
23. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005;96:399-409.
24. Nagata K, Imai T, Yamashita T, Tsuda M, TozakiSaitoh H, Inoue K. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain. 2009;5:20.
25. Park HJ, Moon DE. Pharmacologic management of chronic pain. Korean J Pain. 2010;23:99-108.
26. Can OD, Altintop MD, Ozkay UD, Uçel UI, Doğruer B, Kaplancikli ZA. Synthesis of thiadiazole derivatives bearing hydrazone moieties and evaluation of their pharmacological effects on anxiety, depression, and nociception parameters in mice. Arch Pharm Res. 2012;35:659-69.
27. Kaplancikli ZA, Turan-Zitouni G, Ozdemir A, Can OD, Chevallet P. Synthesis and antinociceptive activities of some pyrazoline derivatives. Eur J Med Chem. 2009;44:2606-10.
28. D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72:74-9.
29. Adeyemi OO, Okpo SO, Okpaka O. The analgesic effect of the methanolic extract of Acanthus montanus. J Ethnopharmacol. 2004;90:45-8.
30. Özkay ÜD, Can ÖD, Kaplancıklı ZA. Antinociceptive activities of some triazole and pyrazoline moieties-bearing compounds. Med Chem Res. 2012;21:1056-61.
31. Woolfe G, Mcdonald AD. The evaluation of analgesic action of pethidine hydrochloride (Demerol). J Pharmacol Exp Ther. 1944;80:300-7.
32. Gabra BH, Sirois P. Beneficial effect of chronic treatment with the selective bradykinin B1 receptor antagonists, R-715 and R-954, in attenuating streptozotocin-diabetic thermal hyperalgesia in mice. Peptides. 2003;24:1131-9.
33. de Fátima Arrigoni-Blank M, Dmitrieva EG, Franzotti EM, Antoniolli AR, Andrade MR, Marchioro M. Anti-inflammatory and analgesic activity of Peperomia pellucida (L.) HBK (Piperaceae). J Ethnopharmacol. 2004;91:215-8.
34. Ridtitid W, Sae-Wong C, Reanmongkol W, Wongnawa M. Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals. J Ethnopharmacol. 2008;118:225-30.
35. Pavin NF, Donato F, Cibin FW, Jesse CR, Schneider PH, de Salles HD et al. Antinociceptive and antihypernociceptive effects of Se-phenyl thiazolidine-4- carboselenoate in mice. Eur J Pharmacol. 2011;668:169-76.
36. Koster R. Anderson M. De Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:412-5.
37. Demir Özkay U, Can OD. Anti-nociceptive effect of vitexin mediated by the opioid system in mice. Pharmacol Biochem Behav. 2013;109:23-30.
38. Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics. J Neurosci Methods. 1985;14:69-76.
39. Ruangsang P, Tewtrakul S, Reanmongkol W. Evaluation of the analgesic and anti-inflammatory activities of Curcuma mangga Val and Zijp rhizomes. J Nat Med. 2010;64:36-41.
40. Rogers DC, Jones DN, Nelson PR, Jones CM, Quilter CA, Robinson TL et al. Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains. Behav Brain Res. 1999;105:207-17.
41. Pollak D, Weitzdoerfer R, Yang YW, Prast H, Hoeger H, Lubec G. Cerebellar protein expression in three different mouse strains and their relevance for motor performance. Neurochem Int. 2005;46:19-29.
42. Wong CH, Dey P, Yarmush J, Wu WH, Zbuzek VK. Nifedipine-induced analgesia after epidural injection in rats. Anesth Analg. 1994;79:303-6.
43. De Souza MM, Pereira MA, Ardenghi JV, Mora TC, Bresciani LF, Yunes RA et al. Filicene obtained from Adiantum cuneatum interacts with the cholinergic, dopaminergic, glutamatergic, GABAergic, and tachykinergic systems to exert antinociceptive effect in mice. Pharmacol Biochem Behav. 2009;93:40-6.
44. Park SH, Sim YB, Kang YJ, Kim SS, Kim CH, Kim SJ et al. Hop extract produces antinociception by acting on opioid system in mice. Korean J Physiol Pharmacol. 2012;16:187-92.
45. Coelho LP, Reis PA, de Castro FL, Gayer CR, da Silva Lopes C, da Costa e Silva MC et al. Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds. J Ethnopharmacol. 2005;98:109-16.
46. Pinheiro MM, Bessa SO, Fingolo CE, Kuster RM, Matheus ME, Menezes FS et al. Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves. J Ethnopharmacol. 2010;127:407-13.
47. Pinheiro MM, Boylan F, Fernandes PD. Antinociceptive effect of the Orbignya speciosa Mart. (Babassu) leaves: evidence for the involvement of apigenin. Life Sci. 2012;91:293-300.
48. Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain. 1992;51:5-17.
49. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and noninflammatory pain. Pain. 1987;30:103-14.
50. Kanjhan R. Opioids and pain. Clin Exp Pharmacol Physiol. 1995;22:397-403.
51. Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001;53:597-652.
52. Testa B, Crivori P, Reist M, Carrupt PA. The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples. Perspect Drug Discov Des. 2000;19:179-211.
53. Patil M, Hunoor R, Gudasi K. Transition metal complexes of a new hexadentate macroacyclic N2O4- donor Schiff base: inhibitory activity against bacteria and fungi. Eur J Med Chem. 2010;45:2981-86.

APA	AKAN B, DEMİR Ü (2019). Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. , 729 - 744. 10.17826/cumj.490690
Chicago	AKAN Bürge Doğruer,DEMİR Ümide Özkay Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. (2019): 729 - 744. 10.17826/cumj.490690
MLA	AKAN Bürge Doğruer,DEMİR Ümide Özkay Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. , 2019, ss.729 - 744. 10.17826/cumj.490690
AMA	AKAN B,DEMİR Ü Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. . 2019; 729 - 744. 10.17826/cumj.490690
Vancouver	AKAN B,DEMİR Ü Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. . 2019; 729 - 744. 10.17826/cumj.490690
IEEE	AKAN B,DEMİR Ü "Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri." , ss.729 - 744, 2019. 10.17826/cumj.490690
ISNAD	AKAN, Bürge Doğruer - DEMİR, Ümide Özkay. "Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri". (2019), 729-744. https://doi.org/10.17826/cumj.490690

APA	AKAN B, DEMİR Ü (2019). Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. Cukurova Medical Journal, 44(3), 729 - 744. 10.17826/cumj.490690
Chicago	AKAN Bürge Doğruer,DEMİR Ümide Özkay Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. Cukurova Medical Journal 44, no.3 (2019): 729 - 744. 10.17826/cumj.490690
MLA	AKAN Bürge Doğruer,DEMİR Ümide Özkay Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. Cukurova Medical Journal, vol.44, no.3, 2019, ss.729 - 744. 10.17826/cumj.490690
AMA	AKAN B,DEMİR Ü Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. Cukurova Medical Journal. 2019; 44(3): 729 - 744. 10.17826/cumj.490690
Vancouver	AKAN B,DEMİR Ü Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri. Cukurova Medical Journal. 2019; 44(3): 729 - 744. 10.17826/cumj.490690
IEEE	AKAN B,DEMİR Ü "Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri." Cukurova Medical Journal, 44, ss.729 - 744, 2019. 10.17826/cumj.490690
ISNAD	AKAN, Bürge Doğruer - DEMİR, Ümide Özkay. "Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri". Cukurova Medical Journal 44/3 (2019), 729-744. https://doi.org/10.17826/cumj.490690