RESEARCH PAPER
Antinociceptive screening of various 1,2,4-triazole-3-thione derivatives in the hot-plate test in mice
1
Department of Pathophysiology, Medical University of Lublin, Poland
2
Isobolographic Analysis Laboratory, Institute of Rural Health, Poland
3
Department of Pharmacology, Medical University of Lublin, Poland
Corresponding author
Jarogniew J. Łuszczki
Department of Pathophysiology, Medical University of Lublin, Department of Pathophysiology, 20-090, Lublin, Poland
Department of Pathophysiology, Medical University of Lublin, Department of Pathophysiology, 20-090, Lublin, Poland
J Pre Clin Clin Res. 2019;13(1):9-12
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Despite the large number of analgesic drugs available currently, pain therapy is still a challenging issue for researchers and clinicians. The search for new drugs that could relieve patients from pain is not only justified, but also highly recommended.
Objective:
This study aimed to perform antinociceptive screening of 4 various 1,2,4-triazole-3-thione derivatives (TPB-2, TPB-4, TPF-32 and TPF-38) in the hot-plate test in mice, which is an experimental model allowing the testing of compounds alleviating acute thermal pain.
Material and methods:
Experimental verification of the antinociceptive effects of the tested compounds (administered intraperitoneally in a constant dose of 300 mg/kg) was performed in the hot-plate test in mice, by calculating maximum possible antinociceptive effects (MPAE in %) at 4 various pretreatment times (15, 30, 60 and 120 min.).
Results:
TPB-2 exerted strong antinociceptive effects with MPAE ranging between 18.54 – 35.43% in the hot-plate test. Similarly, TPF-32 exerted firmly established antinociceptive effects with MPAE ranging from 13.50 – 37.05%. In the case of TPB-4 and TPF-38, both compounds produced slight changes in MPAE in the hot-plate test in mice. These agents can be classified as virtually ineffective in the hot-plate test.
Conclusions:
The screening test revealed that TPB-2 and TPF-32 exerted a clear-cut antinociceptive effect in the hot-plate test in mice. If the results from this study were to be translated to clinical settings, both TPB-2 and TPF-32 might be beneficial drugs for pain relief in humans.
Despite the large number of analgesic drugs available currently, pain therapy is still a challenging issue for researchers and clinicians. The search for new drugs that could relieve patients from pain is not only justified, but also highly recommended.
Objective:
This study aimed to perform antinociceptive screening of 4 various 1,2,4-triazole-3-thione derivatives (TPB-2, TPB-4, TPF-32 and TPF-38) in the hot-plate test in mice, which is an experimental model allowing the testing of compounds alleviating acute thermal pain.
Material and methods:
Experimental verification of the antinociceptive effects of the tested compounds (administered intraperitoneally in a constant dose of 300 mg/kg) was performed in the hot-plate test in mice, by calculating maximum possible antinociceptive effects (MPAE in %) at 4 various pretreatment times (15, 30, 60 and 120 min.).
Results:
TPB-2 exerted strong antinociceptive effects with MPAE ranging between 18.54 – 35.43% in the hot-plate test. Similarly, TPF-32 exerted firmly established antinociceptive effects with MPAE ranging from 13.50 – 37.05%. In the case of TPB-4 and TPF-38, both compounds produced slight changes in MPAE in the hot-plate test in mice. These agents can be classified as virtually ineffective in the hot-plate test.
Conclusions:
The screening test revealed that TPB-2 and TPF-32 exerted a clear-cut antinociceptive effect in the hot-plate test in mice. If the results from this study were to be translated to clinical settings, both TPB-2 and TPF-32 might be beneficial drugs for pain relief in humans.
REFERENCES (38)
1.
Cooper TE, Wiffen PJ, Heathcote LC, Clinch J, Howard R, Krane E, et al. Antiepileptic drugs for chronic non-cancer pain in children and adolescents. Cochrane Database Syst Rev. 2017;8:Cd012536.
2.
Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Buchsbaum R, et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017; 76: 24–31.
3.
Abaza MS, Bahman AM, Al-Attiyah RJ. Valproic acid, an antiepileptic drug and a histone deacetylase inhibitor, in combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic and chemosensitizing effects in human colorectal cancer cells: underlying molecular mechanisms. Int J Mol Med. 2014; 34: 513–532.
4.
Rizzo A, Donzelli S, Girgenti V, Sacconi A, Vasco C, Salmaggi A, et al. In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells. J Exp Clin Cancer Res. 2017; 36: 76.
5.
Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019; 1: Cd007076.
6.
Todorov AA, Kolchev CB, Todorov AB. Tiagabine and gabapentin for the management of chronic pain. Clin J Pain. 2005; 21: 358–361.
7.
Abdel Salam OI, Al-Omar MA, Khalifa NM, Amr Ael G, Abdallah MM. Analgesic and anticonvulsant activities of some newly synthesized trisubstituted pyridine derivatives. Z Naturforsch C. 2013; 68: 264–268.
8.
Al-Omar MA, Amr Ael G, Al-Salahi RA. Anti-inflammatory, analgesic, anticonvulsant and antiparkinsonian activities of some pyridine derivatives using 2,6-disubstituted isonicotinic acid hydrazides. Archiv der Pharmazie. 2010; 343: 648–656.
9.
Said SA, Amr Ael G, Sabry NM, Abdalla MM. Analgesic, anticonvulsant and anti-inflammatory activities of some synthesized benzodiazipine, triazolopyrimidine and bis-imide derivatives. Eur J Med Chem. 2009; 44: 4787–4792.
10.
Brenneman DE, Smith GR, Zhang Y, Du Y, Kondaveeti SK, Zdilla MJ, et al. Small molecule anticonvulsant agents with potent in vitro neuroprotection. J Mol Neurosci. 2012; 47: 368–79.
11.
King AM, De Ryck M, Kaminski R, Valade A, Stables JP, Kohn H. Defining the structural parameters that confer anticonvulsant activity by the siteby-site modification of (R)-N’-benzyl 2-amino-3-methylbutanamide. Journal of medicinal chemistry. 2011; 54: 6432–6442.
12.
Sysak A, Obminska-Mrukowicz B. Isoxazole ring as a useful scaffold in a search for new therapeutic agents. Eur J Med Chem. 2017; 137: 292–309.
13.
Mandegary A, Sharififar F, Abdar M. Anticonvulsant effect of the essential oil and methanolic extracts of Zataria multiflora Boiss. Cent Nerv Syst Agents Med Chem. 2013; 13: 93–7.
14.
Ya’u J, Yaro AH, Malami S, Musa MA, Abubakar A, Yahaya SM, et al. Anticonvulsant activity of aqueous fraction of Carissa edulis root bark. Pharmaceut Biol. 2015; 53: 1329–1338.
15.
Goel RK, Gawande D, Lagunin A, Randhawa P, Mishra A, Poroikov V. Revealing medicinal plants that are useful for the comprehensive management of epilepsy and associated comorbidities through in silico mining of their phytochemical diversity. Planta Med. 2015; 81: 495–506.
16.
Flieger J, Kowalska A, Pizon M, Plech T, Luszczki J. Comparison of mouse plasma and brain tissue homogenate sample pretreatment methods prior to high-performance liquid chromatography for a new 1,2,4-triazole derivative with anticonvulsant activity. J Sep Sci. 2015; 38: 2149–2157.
17.
Flieger J, Pizon M, Plech T, Luszczki JJ. Analysis of new potential anticonvulsant compounds in mice brain tissue by SPE/HPLC/DAD. J Chromatogr B Analyt Technol Biomed Life Sci. 2012; 909: 26–33.
18.
Kapron B, Luszczki J, Paneth A, Wujec M, Siwek A, Karcz T, et al. Molecular mechanism of action and safety of 5-(3-chlorophenyl)-4- hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione – a novel anticonvulsant drug candidate. Int J Med Sci. 2017; 14: 741–749.
19.
Luszczki JJ, Plech T, Wujec M. Influence of 5-(3-chlorophenyl)-4- (4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione on the anticonvulsant action of 4 classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Pharmacol Rep. 2012; 64: 970–978.
20.
Luszczki JJ, Plech T, Wujec M. Effect of 4-(4-bromophenyl)-5- (3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione on the anticonvulsant action of different classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Eur J Pharmacol. 2012; 690: 99–106.
21.
Plech T, Kapron B, Luszczki JJ, Paneth A, Siwek A, Kolaczkowski M, et al. Studies on the anticonvulsant activity of 4-alkyl-1,2,4-triazole3-thiones and their effect on GABAergic system. Eur J Med Chem. 2014; 86: 690–699.
22.
Plech T, Kapron B, Luszczki JJ, Wujec M, Paneth A, Siwek A, et al. Studies on the anticonvulsant activity and influence on GABA-ergic neurotransmission of 1,2,4-triazole-3-thione-based compounds. Molecules. 2014; 19: 11279–11299.
23.
Plech T, Luszczki JJ, Wujec M, Flieger J, Pizon M. Synthesis, characterization and preliminary anticonvulsant evaluation of some 4-alkyl-1,2,4-triazoles. Eur J Med Chem. 2013; 60: 208–215.
24.
Azmi S, ElHadd KT, Nelson A, Chapman A, Bowling FL, Perumbalath A, et al. Pregabalin in the management of painful diabetic neuropathy: a narrative review. Diabetes Ther. 2019; 10: 35–56.
25.
Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br J Anaesth. 2018; 120: 1315–1334.
26.
Smith MD, Woodhead JH, Handy LJ, Pruess TH, Vanegas F, Grussendorf E, et al. Preclinical comparison of mechanistically different antiseizure, antinociceptive, and/or antidepressant drugs in a battery of rodent models of nociceptive and neuropathic pain. Neurochem Res. 2017; 42: 1995–2010.
27.
Luszczki JJ, Kolacz A, Czuczwar M, Przesmycki K, Czuczwar SJ. Synergistic interaction of gabapentin with tiagabine in the formalin test in mice: an isobolographic analysis. Eur J Pain. 2009; 13: 665–672.
28.
Luszczki JJ, Kolacz A, Wojda E, Czuczwar M, Przesmycki K, Czuczwar SJ. Synergistic interaction of gabapentin with tiagabine in the hotplate test in mice: an isobolographic analysis. Pharmacol Rep. 2009; 61: 459–467.
29.
Listos J, Talarek S, Orzelska J, Fidecka S, Wujec M, Plech T. The antinociceptive effect of 4-substituted derivatives of 5-(4-chlorophenyl)- 2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thion e in mice. Naunyn Schmiedebergs Arch Pharmacol. 2014; 387: 367–375.
30.
Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther. 1953; 107: 385–393.
31.
Luszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice. Pharmacol Rep. 2010; 62: 942–948.
32.
Luszczki JJ, Florek-Luszczki M. Synergistic interaction of pregabalin with the synthetic cannabinoid WIN 55,212-2 mesylate in the hotplate test in mice: an isobolographic analysis. Pharmacol Rep. 2012; 64: 723–732.
33.
Luszczki JJ, Czuczwar SJ. Dose-response relationship analysis of vigabatrin doses and their antinociceptive effects in the hot-plate test in mice. Pharmacol Rep. 2008; 60: 409–414.
34.
Schmauss C, Yaksh TL. In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther. 1984; 228: 1–12.
35.
Luszczki JJ, Czuczwar SJ. Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsy. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31: 529–538.
36.
Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007; Chapter 8: Unit 8.9. https://doi.org/10.1002/047114....
37.
Dhouibi R, Moalla D, Ksouda K, Ben Salem M, Hammami S, Sahnoun Z, et al. Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS. Arch Physiol Biochem. 2018; 124: 335–343.
38.
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 2010; 160: 1577–1579.
| eISSN: | 1898-7516 |
| ISSN: | 1898-2395 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
