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Articles

Vol. 1 No. 2 (2010): April– June 2010

Discovery of Isatinimino Derivatives as New Leads for Neuropathic Pain Treatment: An Isomeric Modification Approach

DOI
https://doi.org/10.37285/ijddd.1.2.9
Submitted
November 24, 2024
Published
2010-05-15

Abstract

Isatin, an endogenous compound identified in humans possesses a wide range of biological properties. Among them the most significant being anxiogenic, anticonvulsant and analgesic activities. Neuropathic pain arises due to damage or permanent alteration of the peripheral or central nervous system. The major inhibitory neurotransmitter of the central nervous system (CNS), γ-aminobutyric acid (GABA) has been implicated in the etiology and pharmacotherapy of different neurological and psychiatric disorders including pain and epileptic conditions. Hence, the present study is aimed at design and synthesis of newer isatinimino GABA derivatives useful in the treatment of neurological disorders like neuropathic pain and epilepsy. Various isatinimino GABA amides were synthesized and screened for peripheral analgesic, antiallodynic, antihyperalgesic and anticonvulsant activities. The structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. The synthesized derivatives of the inhibitory neurotransmitter GABA produced anticonvulsant and antinociceptive actions in the acetic acid induced writhing test and in two peripheral nerve injury models of neuropathic pain.

References

  1. [1] Glover, V.; Halket, J.M.; Watkins, P.J.; Clow, A.; Goddwin, B.L.; Sandler, M. J. Neurochemistry 1988, 51, 656.
  2. [2] Palit, G.; Kumar, R.; Patnaik, G.K.; Bhattacharya, S.K. Biogenic Amines 1997, 13, 131.
  3. [3] McIntyre, I.M.; Norman, T.R. J. Neural Transm. 1990, 79, 35.
  4. [4] Matheus, M.E.; Violante, F.A.; Garden, S.J.; Pinto, A.C.; Fernandes, P.D. Eur. J. Pharmacol. 2007, 556, 200.
  5. [5] Ueda, H.; Rashid, M.H. Drug News Perspect. 2003, 16, 605.
  6. [6] Jensen, S.T. Eur. J. Pain. 2002, 6, 61.
  7. [7] Rogawski, M.A.; Loscher, W. Neuroscience. 2004, 5, 553.
  8. [8] Sindrup, S.H.; Jensen, T.S. Pain. 1999, 83, 389-400.
  9. [9] Sivilotti, L.; Nistri, A. Prog. Neurobiol. 1991, 36, 35.
  10. [10] Meldrum, B.S. Int. Rev. Neurobiol. 1975, 17, 1.
  11. [11] Loscher, W. In Epilepsy and GABA Receptor Agonists: Basic and Therapeutic Research (L.E.R.S. Monograph Series); Bartholini, G., Bossi, L., Lloyd, K.G., Morselli,P. L., Eds.; Raven Press: New York, 1985; p 109.
  12. [12] Meldrum, B. In Current and Future Trends in Anticonvulsant, Anxiety and Stroke Therapy; Wiley-Liss Inc.: New York, 1990; p 31.
  13. [13] Hwang, J.H.; Yaksh, T.L. Pain.1997, 70, 15.
  14. [14] Alves, N.D.; De Castro, C.C.M.; De Carvalho, A.M.; Santos, F.J.C.; Silveira, D.G. Arq. Neuropsiquiatr. 1999, 57, 916.
  15. [15] Serpell, M.G. Pain. 2002, 99, 557.
  16. [16] Yogeeswari, P.; Ragavendran, J.V.; Sriram, D.; Nageswari, Y.; Kavya, R.; Sreevatsan, N.; Vanitha, K.; Stables, J.P. J. Med. Chem. 2007, 50, 2459.
  17. [17] Yogeeswari, P.; Ragavendran, J.V.; Sriram, D.; Kavya, R.; Vanitha, K.; Harshini, N. Pharmacol. 2007, 81, 21.
  18. [18] Ragavendran, J.V.; Sriram, D.; Patel, S.K.; Reddy, I.V.; Bharathwajan, N.; Stables, J.; Yogeeswari, P. Eur.J. Med. Chem. 2007, 42, 146.
  19. [19] Krall, R. L.; Penry, J. K.; White, B. G.; Kupferberg, H. J.; Swinyard, E. A. Epilepsia.1978, 19, 409.
  20. [20] Porter, R. J.; Cereghino, J. J.; Gladding, G. D.; Hessie, B. J.; Kupferberg, H. J.; Scoville, B.; White, B. Cleveland Clin. Quart. 1984, 51, 293.
  21. [21] Kupferberg, H.J. Epilepsia. 1986, 30, S51.
  22. [22] Khan, S. A.; Siddiqui, A. A.; Bhatt, S. Asian J. Chem. 2002, 14, 1117.
  23. [23] Sridhar, S. K.; Ramesh, A.. Biol. Pharm. Bull. 2001, 24, 1149.
  24. [24] Chakraborty, A; Devi, R.K.B.; Rita, S.; Sharatchandra,K. H.; Singh, T.H.I. Indian J. Pharmacol. 2004, 36, 148.
  25. [25] Belelli, D.; Bolger, M. B.; Gee, K. W. Eur. J. Pharmacol. 1989, 166, 325.
  26. [26] Barrada, O.; Oftedal, S. I. Neurophysiol. 1970, 29, 220.
  27. [27] Jiang, W.; Duong, T.M.; De Lanerolle, N.C. Epilepsia. 1999, 40, 5.
  28. [28] Siegmund, E.A.; Cadmus, R.A.Proc. Soc. Exp. Biol. 1957, 95, 729.
  29. [29] Bennett, G.J.; Xie, Y.K. Pain. 1988, 33, 87.
  30. [30] Kim, S.; Chung, J.M.. Pain. 1992, 50, 355.
  31. [31] Choi, Y.; Yoon, Y.W.; Na, H.S.; Kim, S.H.; Chung, J.M.. Pain. 1994, 59, 369
  32. [32] Field, M.J.; Bramwell, S.; Hughes, J.; Singh, L. Pain. 1999, 83, 303.
  33. [33] Field, M.J.; McCleary, S.; Hughes, J.; Singh, L.. Pain. 1999, 80, 391.
  34. [34] Caudle, R.M.; Mannes, A.J.; Benoliel, R.; Eliav, E.; Iadarola, M.J. J. Pain. 2001, 2, 118.
  35. [35] Gonzalez, M.I.; Field, M.J.; Hughes, J.; Singh, L. J. Pharmacol. Exp. Ther. 2000, 294, 444.