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Recent Advances in Inflammation & Allergy Drug Discovery

Author(s): Asghar Davood*, Atefeh Saadabadi, Porya Torkaman, Ehsan Salehi and Hamed Shafaroodi

DOI: 10.2174/2772270817666230302145537

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In vivo Analgesic Activity of New N-arylphthalimides Derivatives in Mice

Page: [121 - 126] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background: A series of phthalimides related to thalidomide have been studied for analgesic activity in the formalin test. The formalin test was performed in mice in a nociceptive pattern to evaluate analgesic activity.

Methods: In this study, nine derivatives of phthalimides were evaluated in terms of exerting analgesic effects in mice. They exerted significant analgesic effects compared to indomethacin and negative control. These compounds were synthesized and characterized by TLC, followed by IR and H1NMR in the previous studies. Two distinct periods of high licking activity were used to analyze both acute and chronic pain. All compounds were compared with indomethacin and carbamazepine as positive control and vehicle as a negative control.

Results: All of the tested compounds exhibited significant analgesic activity in both the first and second phases of the test compared to the control group (DMSO), although they did not show more activity than the reference drug (indomethacin) but were comparable to indomethacin.

Conclusion: This information may be useful in the development of a more potent phthalimide as an analgesic agent that acts as a sodium channel blocker and COX inhibitor.

Graphical Abstract

[1]
Lynch T, Connor S, Clark D. Mapping levels of palliative care development: A global update. J Pain Symptom Manage 2013; 45(6): 1094-106.
[http://dx.doi.org/10.1016/j.jpainsymman.2012.05.011] [PMID: 23017628]
[2]
Palliative care. Fact sheet N°402. Available from: http://www.who.int/mediacentre/factsheets/fs402/en/ (Accessed on: July 2015).
[3]
Seya MJ, Gelders SFAM, Achara OU, Milani B, Scholten WK. A first comparison between the consumption of and the need for opioid analgesics at country, regional, and global levels. J Pain Palliat Care Pharmacother 2011; 25(1): 6-18.
[http://dx.doi.org/10.3109/15360288.2010.536307] [PMID: 21426212]
[4]
Chabal C, Jacobson L, Mariano A, Chaney E, Britell CW. The use of oral mexiletine for the treatment of pain after peripheral nerve injury. Anesthesiology 1992; 76(4): 513-7.
[http://dx.doi.org/10.1097/00000542-199204000-00005] [PMID: 1312797]
[5]
Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988; 331(8575-8576): 9-11.
[http://dx.doi.org/10.1016/S0140-6736(88)90999-3] [PMID: 2891940]
[6]
Kastrup J, Angelo H, Petersen P, Dejgård A, Hilsted J. Treatment of chronic painful diabetic neuropathy with intravenous lidocaine infusion. BMJ 1986; 292(6514): 173.
[http://dx.doi.org/10.1136/bmj.292.6514.173] [PMID: 3080123]
[7]
McQuay H, Carroll D, Jadad AR, Wiffen P, Moore A. Anticonvulsant drugs for management of pain: A systematic review. BMJ 1995; 311(7012): 1047-52.
[http://dx.doi.org/10.1136/bmj.311.7012.1047] [PMID: 7580659]
[8]
Abram SE, Yaksh TL. Systemic lidocaine blocks nerve injury-induced hyperalgesia and nociceptor-driven spinal sensitization in the rat. Anesthesiology 1994; 80(2): 383-91.
[http://dx.doi.org/10.1097/00000542-199402000-00018] [PMID: 8311320]
[9]
Chaplan SR, Bach FW, Shafer SL, Yaksh TL. Prolonged alleviation of tactile allodynia by intravenous lidocaine in neuropathic rats. Anesthesiology 1995; 83(4): 775-85.
[http://dx.doi.org/10.1097/00000542-199510000-00017] [PMID: 7574057]
[10]
Koch BD, Faurot GF, McGuirk JR, Clarke DE, Hunter JC. Modulation of mechano-hyperalgesia by clinically effective analgesics in rats with a peripheral mononeuropathy. Analgesia (Elmsford N Y) 1996; 2: 157-64.
[11]
Hales BF. Thalidomide on the comeback trail. Nat Med 1999; 5(5): 489-90.
[http://dx.doi.org/10.1038/8371] [PMID: 10229222]
[12]
Hashimoto Y. Novel biological response modifiers derived from thalidomide. Curr Med Chem 1998; 5(3): 163-78.
[http://dx.doi.org/10.2174/0929867305666220314203435] [PMID: 9562600]
[13]
Vargesson N. Thalidomide-induced teratogenesis: History and mechanisms. Birth Defects Res C Embryo Today 2015; 105(2): 140-56.
[http://dx.doi.org/10.1002/bdrc.21096] [PMID: 26043938]
[14]
Noguchi T, Shimazawa R, Nagasawa K, Hashimoto Y. Thalidomide and its analogues as cyclooxygenase inhibitors. Bioorg Med Chem Lett 2002; 12(7): 1043-6.
[http://dx.doi.org/10.1016/S0960-894X(02)00084-7] [PMID: 11909713]
[15]
Rajkumar SV. Current status of thalidomide in the treatment of cancer. Oncology (Williston Park) 2001; 15(7): 867-74.
[PMID: 11499688]
[16]
Vamecq J, Bac P, Herrenknecht C, Maurois P, Delcourt P, Stables JP. Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore. J Med Chem 2000; 43(7): 1311-9.
[http://dx.doi.org/10.1021/jm990068t] [PMID: 10753468]
[17]
Iman M, Saadabadi A, Davood A. Docking studies of phthalimide pharmacophore as a sodium channel blocker. Iran J Basic Med Sci 2013; 16(9): 1016-21.
[PMID: 24171082]
[18]
Iman M, Saadabadi A, Davood A. Molecular docking analysis and molecular dynamics simulation study of ameltolide analogous as a sodium channel blocker. Turk J Chem 2015; 39: 306-16.
[http://dx.doi.org/10.3906/kim-1402-37]
[19]
Iman M, Shafaroodi H, Davood A, et al. Design and synthesis of 2- (arylmethylideneamino) isoindolines as new potential analgesic and anti inflammatory agents: A molecular hybridization approach. Curr Pharm Des 2016; 22(37): 5760-6.
[http://dx.doi.org/10.2174/1381612822666160701072127] [PMID: 27396602]
[20]
Banaroiee N, Davood A, Iman M, Shafaroodi H. Shafiee; A.; N-arylmethylideneaminophthalimide: Design, synthesis and evaluation as analgesic and anti-inflammatory agents, Mini-reviews in Med. Chem 2019; 19(8): 679-87.
[21]
Davood A, Azimidoost L, Shafaroodi H, et al. docking and synthesis of 2-arylisoindoline-1,3-dione derivatives as anticonvulsant agents. Pharm Chem J 2014; 48(3): 175-80.
[http://dx.doi.org/10.1007/s11094-014-1073-z]
[22]
Davood A, Amini M, Azimidoost L, et al. Docking, synthesis, and pharmacological evaluation of isoindoline derivatives as anticonvulsant agents. Med Chem Res 2013; 22(7): 3177-84.
[http://dx.doi.org/10.1007/s00044-012-0256-y]
[23]
Davood A, Shafaroodi H, Amini M, Nematollahi A, Shirazi M, Iman M. Design, synthesis and protection against pentylenetetrazole-induced seizure of N-aryl derivatives of the phthalimide pharmacophore. Med Chem 2012; 8(5): 953-63.
[http://dx.doi.org/10.2174/157340612802084289] [PMID: 22741781]
[24]
Davood A, Pouriaiee H, Shafaroodi H, et al. New derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models. Iran J Basic Med Sci 2017; 20(4): 430-7.
[PMID: 28804613]
[25]
Saadabadi A, Kohen B, Irandoust M, et al. 2, 5-Disubstituted phthalimides: Design, synthesis and anticonvulsant activity in scPTZ and MES models. Curr Computeraided Drug Des 2018; 14(4): 310-21.
[http://dx.doi.org/10.2174/1573409914666180516115450] [PMID: 29766822]
[26]
Taghizad S, Behbahaninia K, Hadipour M, Davood A. Design and synthesis of new derivatives of Pyrrolopyridine and Isoindole as potential anticonvulsant agents. Curr Comput Aided Drug Des 2022; 18(3): 159-67.
[http://dx.doi.org/10.2174/1573409918666220512000247] [PMID: 35546772]
[27]
Iman M, Fakhari S, Jahanpanah M, Naderi N, Davood A. Design and Synthesis of 4-flurophthalimides as potential anticonvulsant agents. Iran J Pharm Res 2018; 17(3): 896-905.
[PMID: 30127813]
[28]
Iman M, Saadabadi A, Davood A, et al. Docking, Synthesis and anticonvulsant activity of N-substituted isoindoline-1,3-dione. Iran J Pharm Res 2017; 16(2): 586-95.
[PMID: 29721024]
[29]
Dubuisson D, Dennis SG. The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977; 4(2) (Suppl. C): 161-74.
[http://dx.doi.org/10.1016/0304-3959(77)90130-0] [PMID: 564014]
[30]
Regalado AI, Mancebo B, Paixão A, López Y, Merino N, Sánchez LM. Antinociceptive activity of methanol extract of tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. Stems. Med Princ Pract 2017; 26(4): 368-74.
[http://dx.doi.org/10.1159/000478015] [PMID: 28591753]