Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models

Ann N Y Acad Sci. 2002 Jun;967:482-9. doi: 10.1111/j.1749-6632.2002.tb04306.x.


Bimoclomol (BML), a symptomatic antidiabetic agent, has been developed by Biorex R & D Co. to treat diabetic neuropathy and retinopathy. BRX-220, an orally active member of the BRX family, has been developed to treat diabetic complications and insulin resistance (IR) as a follow-up compound. The effect of BRX-220 on peripheral neuropathy was examined in rats with diabetes (type 1) induced by administration of a beta-cell toxin, streptozotocin (STZ, 45 mg/kg iv). Nerve functions were evaluated by electrophysiological measurements of muscle motor and sensory nerve conduction velocities (MNCV and SNCV, respectively). MNCV and SNCV decreased in diabetic rats by 25% (p < 0.001). A 1-month preventive treatment with BRX-220 (2.5, 5, 10, and 20 mg/kg po) dose-dependently improved diabetes-related deficits in MNCV (51.3%, 71.3%, 86.1%, and 91.3%) and SNCV (48.9%, 68.5%, 86.1%, and 93.2%). Insulin sensitivity was measured using the insulin tolerance test (ITT), both in STZ diabetic and in Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). Severe IR was detected in STZ diabetic and ZDF rats. This resistance was significantly (p < 0.05) reduced by BRX-220 treatment.

MeSH terms

  • Animals
  • Diabetic Neuropathies / drug therapy*
  • Guanidines / pharmacology
  • Hydroxylamines / therapeutic use*
  • Hypoglycemic Agents / pharmacology
  • Insulin Resistance*
  • Male
  • Metformin / pharmacology
  • Pioglitazone
  • Rats
  • Rats, Wistar
  • Rats, Zucker
  • Streptozocin
  • Thiazoles / pharmacology
  • Thiazolidinediones*


  • Guanidines
  • Hydroxylamines
  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • Streptozocin
  • Metformin
  • arimoclomol
  • pimagedine
  • Pioglitazone