Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy

Life Sci. 2008 Mar 12;82(11-12):570-6. doi: 10.1016/j.lfs.2007.11.031. Epub 2007 Dec 26.


Peripheral diabetic neuropathy is a heterogeneous group of disorders, and is known to affect 50-60% of diabetic patients. Poly (ADP-ribose) polymerase (PARP) activation has been identified as one of the key components in the pathogenesis of diabetic neuropathy. In the present study we have targeted PARP overactivation in diabetic neuropathy using a known PARP inhibitor, 4 amino 1, 8-napthalimide (4-ANI). Streptozotocin induced diabetic rats developed neuropathy within 6 weeks, which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) along with neuropathic pain and abnormal sensory perception. Six weeks after diabetes induction Sprague Dawley rats were treated with 4-ANI (3 and 10 mg/kg, p.o.) for a period of two weeks (seventh and eighth weeks). Two week treatment with 4-ANI showed improvement in nerve conduction, nerve blood flow and reduction in tail flick responses and mechanical allodynia in diabetic animals. 4-ANI also attenuated PAR immunoreactivity and NAD depletion in nerves of diabetic animals. Results of present study suggest the potential of PARP inhibitors like 4-ANI in the treatment of diabetic neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Naphthylamine / analogs & derivatives*
  • 1-Naphthylamine / chemistry
  • 1-Naphthylamine / metabolism
  • 1-Naphthylamine / pharmacology
  • 1-Naphthylamine / therapeutic use
  • Animals
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / enzymology
  • Diabetic Neuropathies / enzymology*
  • Humans
  • Male
  • NAD / metabolism
  • Naphthalimides / chemistry
  • Naphthalimides / metabolism*
  • Naphthalimides / pharmacology
  • Naphthalimides / therapeutic use*
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Pain Measurement
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Quinolones / chemistry
  • Quinolones / metabolism*
  • Quinolones / pharmacology
  • Quinolones / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin


  • Naphthalimides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Quinolones
  • NAD
  • 4-amino-1,8-naphthalimide
  • Streptozocin
  • 1-Naphthylamine
  • Poly(ADP-ribose) Polymerases