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Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri

Year 2019, Volume: 44 Issue: 3, 729 - 744, 30.09.2019
https://doi.org/10.17826/cumj.490690

Abstract

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. 


References

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  • 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, p. 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:S105-20.
  • 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)-N-methylbenzamide]. I. A mixed opioid agonist with potent antinociceptive activity. J Pharmacol Exp Ther. 2003;307:1221-6.
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  • 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, Tozaki-Saitoh 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. Pavin NF, Donato F, Cibin FW, Jesse CR, Schneider PH, de Salles HD et al. Antinociceptive and anti-hypernociceptive effects of Se-phenyl thiazolidine-4-carboselenoate in mice. Eur J Pharmacol. 2011;668:169-76.
  • 35. Koster R. Anderson M. De Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:412-5.
  • 36. Demir Özkay U, Can OD. Anti-nociceptive effect of vitexin mediated by the opioid system in mice. Pharmacol Biochem Behav. 2013;109:23-30.
  • 37. Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics. J Neurosci Methods. 1985;14:69-76.
  • 38. 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.
  • 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 non-inflammatory 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, P. A., The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples, Perspect Drug Discov. Des., 19, 179-211 (2000).
  • 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., 45, 2981-2986 (2010).

The antinociceptive effects of some piperazine alkanol derivatives

Year 2019, Volume: 44 Issue: 3, 729 - 744, 30.09.2019
https://doi.org/10.17826/cumj.490690

Abstract

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. 


References

  • 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 NO-cGMP-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, p. 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:S105-20.
  • 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)-N-methylbenzamide]. 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, Tozaki-Saitoh 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. Pavin NF, Donato F, Cibin FW, Jesse CR, Schneider PH, de Salles HD et al. Antinociceptive and anti-hypernociceptive effects of Se-phenyl thiazolidine-4-carboselenoate in mice. Eur J Pharmacol. 2011;668:169-76.
  • 35. Koster R. Anderson M. De Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:412-5.
  • 36. Demir Özkay U, Can OD. Anti-nociceptive effect of vitexin mediated by the opioid system in mice. Pharmacol Biochem Behav. 2013;109:23-30.
  • 37. Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics. J Neurosci Methods. 1985;14:69-76.
  • 38. 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.
  • 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 non-inflammatory 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, P. A., The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples, Perspect Drug Discov. Des., 19, 179-211 (2000).
  • 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., 45, 2981-2986 (2010).
There are 53 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research
Authors

Bürge Doğruer Akan This is me 0000-0002-5896-609X

Ümide Demir Özkay 0000-0002-6773-4266

Publication Date September 30, 2019
Acceptance Date December 27, 2018
Published in Issue Year 2019 Volume: 44 Issue: 3

Cite

MLA Doğruer Akan, Bürge and Ümide Demir Özkay. “Bazı Piperazin Alkanol türevlerinin Antinosiseptif Etkinlikleri”. Cukurova Medical Journal, vol. 44, no. 3, 2019, pp. 729-44, doi:10.17826/cumj.490690.