Preclinical screening of a novel compound, 2-chlorothiophene for analgesic activity in swiss albino mice
Keywords:Analgesic, Eddy’s hot plate, Formalin test, Thiophene, 2-chlorothiophene
Background: Pain is often the first indication of disease or injury. Analgesics are the drugs used clinically for controlling pain. They relieve pain as a symptom, without affecting its cause. Currently available options are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics for the management of pain. Long term use of existing analgesics causes significant disturbances in the body system. A search for new, safe and cost effective analgesic compound is in progress. Hence a study on 2-chlorothiophene, a novel compound has been carried out in different experimental animal models.
Methods: The central analgesic activity of 2-chlorothiophene was evaluated by eddy’s hot plate method and compared to standard central analgesic, morphine. Both central and peripheral analgesic activities of 2-chlorothiophene were evaluated by formalin induced paw licking in mice and compared to a standard drug, aspirin.
Results: There were 40mg/kg dose of 2-chlorothiophene has shown maximum Pain Inhibition Percentage (PIP) of 46.15% at 60 min compared to 128% by morphine in eddy’s hot plate method. Under Formalin test, 20mg/kg dose of 2-chlorothiophene has shown maximum PIP of 22.91% in early phase and 52.63% in late phase compared to 12.5% and 47.37% by aspirin. The results were statistically significant with p<0.05.
Conclusions: 2-chlorothiophene found to have minimal central analgesic activity and significant peripheral analgesic activity as evident in eddy’s hot plate and formalin tests.
Part III: Pain Terms, A Current List with Definitions and Notes on Usage. Classification of Chronic Pain, Second Edition, IASP Task Force on Taxonomy, edited by H. Merskey and N. Bogduk, IASP Press, Seattle; 1994:209-217. Available at: http://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Pain. Accessed 21 June 2018.
Pain and analgesics. In: Peter N Bennett, Morris J Brown, Pankaj Sharma. Clinical Pharmacology. 11th Ed. Edinburgh: Churchill Livingstone Elsevier;2012:277-93.
Torres Rde C, Marques KS, Leal Kde N, Rocha-Filho PA. Main reasons for medical consultations in family healthcare units in the city of Recife, Brazil: a cross-sectional study. Sao Paulo Med J.2015;133(4):367-70.
Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EB, Kvarstein G, Stubhaug A. Assessment of pain. British J anaesthesia. 2008 Jul 1;101(1):17-24.
Lohman d, Schleifer r, Amon JJ. Access to pain treatment as a human right. BMC Medicine. 2010;8:8.
Srinivasa RV, Saravanan J, Mohan S. Synthesis of 2-Substituted-amino-3-(No-tolylcarboxamido)-4, 5-dimethyl thiophenes as analgesic and anti-inflammatory agents. Ind J Hetero Chem. 1998;8:59-62.
Ahmed MM, Khan MA, Rainsford KD. Synthesis of thiophene and NO-curcuminoids for antiinflammatory and anti-cancer activities. Molecules. 2013 Jan 25;18(2):1483-501.
Revannasiddaiah N, Kumar CA, Kumar GS, Revannaswamy a. Screening of Novel 4-chlorothiophene Compound for Anti-inflammatory Activity in Rats. Pharmacologia. 2014;5(8):316-20.
W Wardakhan WA, Abdel-Salam OM, Elmegeed GA. Screening for antidepressant, sedative and analgesic activities of novel fused thiophene derivatives. Acta Pharmaceutica. 2008;58(1):1-4.
Common Laboratory Animals. In: Ghosh MN. Fundamentals of Experimental Pharmacology. 6th Ed. Kolkata: Ghosh SK and Others;2015:1-13.
Central Analgesic Activity In: Vogel HG, Vogel WH, editors. Drug discovery and evaluation: pharmacological assays. Springer Science & Business Media. 3rd Ed. Newyork: Springer-Verlag Berlin Heidelberg; 2008:984-1030.
Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl-and dithienylbutylamines. J Pharmacol Exp Ther. 1953 Mar 1;107(3):385-93.
Tambe DA, Chaudhari TB, Chaudhari S. Analgesic activity of Caralluma adscendens roxb.(Aerial parts). Int J Pharm Res Dev. 2010;7:10-4.
Nobre ME, Correia AO, Borges Mde B, Sampaio TM, Chakraborty SA, Goncalves Dde O, et al. Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses. Nutr Res. 2013;33(5):422-33.
Charkhpour M, Nayebi AR, Doustar Y, Hassanzadeh K. 8-OH-DPAT prevents morphine-induced apoptosis in rat dorsal raphe nucleus: a possible mechanism for attenuating morphine tolerance. Anesthesia & Analgesia. 2010 Nov 1;111(5):1316-21.
Nikajoo LT. Analgesic activity of aqueous and alcohol root extracts of Pergularia daemia (forsk.) chiov. Int J Pharm Pharm Sci. 2009 Nov;1(Suppl 1):33-7.
Bhutia YD, Vijayaraghavan R, Pathak U. Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice. Indian J pharmacology. 2010 Feb;42(1):17.
Shanmugasundaram P, Venkataraman S. Anti-nociceptive activity of Hygrophila auriculata (Schum) Heine. African Journal of Traditional, Complementary and Alternative medicines (AJTCAM). 2006 Jan 7;2(1):62-9.
Okuda K, Sakurada C, Takahashi M, Yamada T, Sakurada T. Characterization of nociceptive responses and spinal releases of nitric oxide metabolites and glutamate evoked by different concentrations of formalin in rats. Pain. May 2001;92(1-2):107-15
Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 1987;30(1):103-14.
Gholami M, Saboory E, Mehraban S, Niakani A, Banihabib N, Azad MR, Fereidoni J. Time dependent antinociceptive effects of morphine and tramadol in the hot plate test: using different methods of drug administration in female rats. Iranian J pharmaceutical research: IJPR. 2015;14(1):303.
President’s Message. Access to Pain Management - Still Very Much a Human Right. Pain Medicine. 2016;17:1785-89.