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  • Title: Newer N-phthaloyl GABA derivatives with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.
    Author: Yogeeswari P, Ragavendran JV, Sriram D, Kavya R, Vanitha K, Neelakantan H.
    Journal: Pharmacology; 2008; 81(1):21-31. PubMed ID: 17785996.
    Abstract:
    BACKGROUND: There is considerable research evidence supporting a palliative role for gamma-aminobutyric acid (GABA)-ergic neurotransmission and voltage-gated sodium channel blockade in neuropathic pain conditions. Hence, the present study was undertaken to assess the peripheral analgesic, antiallodynic and antihyperalgesic activities of the synthesized structural analogues of GABA. METHODS: The screening study included acute tissue injury, chronic constriction injury (CCI), and spinal nerve ligation (SNL) models of neuropathic pain. RESULTS: All of the tested compounds sup-pressed the acetic acid-induced writhing response significantly in comparison to the control. In particular, compound JVP-8 was observed to be the most active compound with percent inhibition greater than that of the standard drug aspirin (97.8% inhibition of writhing response as against 97.0% shown by aspirin). In neuropathic pain studies, compound JVP-5 (100 mg/kg i.p.) emerged as the most active compound affording maximum protection against dynamic allodynia and mechanical hyperalgesia in the CCI model, and against spontaneous pain and mechanical hyperalgesia in SNL rats. CONCLUSION: In this study, we have demonstrated that combining phthalimide pharmacophore with GABA has evolved compounds effective for the treatment of neuropathic pain.
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