4-((3-(1-6-dihyro-6-oxo-9h-purin-9-yl)-1-oxopropyl)amino)benzoic-acid and Diabetic-Neuropathies

We investigated the ability of Neotrofin, an agent that enhances endogenous nerve growth factor (NGF) levels, to prevent phenotypic, functional and structural changes that occur in the peripheral nerve of streptozotocin-diabetic rats. Eight weeks of Neotrofin treatment prevented depletion of NGF protein in plantar foot skin and sciatic nerve of diabetic rats and increased NGF protein in associated skeletal muscles. These effects were accompanied by maintenance of normal nerve levels of the neuropeptides substance P and calcitonin gene related peptide. Thermal hypoalgesia and conduction slowing of large sensory fibres in diabetic rats were ameliorated by Neotrofin treatment, whereas there was no effect on conduction slowing in large motor fibres or on reduced myelinated fibre axonal calibre. Enhancing endogenous production of neurotrophic factors using small molecules may be an alternative to either exogenous treatment with neurotrophic factors or gene therapy as a therapeutic approach to treating diabetic neuropathy.

Topics: Aminobenzoates; Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Female; Hypoxanthines; Nerve Growth Factor; Neural Conduction; Neurons, Afferent; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Skin; Spinal Nerve Roots; Streptozocin; Substance P; Time Factors