Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: relief of pain and improved somatic and autonomic nerve function.
11 patients with severely painful diabetic neuropathy previously unresponsive to numerous drugs were treated with an aldose reductase inhibitor ('Sorbinil'--Pfizer CP 45, 634); 8 also received a placebo. Response was assessed according to a 0-20 graphic rating scale for pain and by tests for motor and sensory nerve conduction velocities (NCV) and cardiac autonomic nerve function. 8 patients had moderate to marked relief of symptoms, generally beginning on the 3rd or 4th day of medication, 2 had equivocal responses, and 1 had no change. Each of 4 patients with diabetic amyotrophy reported striking improvement in pain and mild to moderate improvement in proximal leg muscle strength; 2 of these noticed improved sensory perception in their feet. Objective evidence of improved muscle strength was obtained in each of these 4 patients and of improved sensation in 3. On stopping medication, pain worsened in 7 of 8 responders, although generally with some delay, suggesting a carry over effect. During the course of treatment autonomic nerve function improved significantly in 6 of 7 patients tested and across the group, and NCV improved in 4 of 7 tested. Both of these variables deteriorated after withdrawal of the drug. A correlation between NCV response and clinical response was apparent. Very little toxicity was observed. These observations suggest that aldose reductase inhibitors may be important in the treatment of symptomatic somatic and autonomic neuropathies complicating diabetes.
D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001341:Autonomic Nervous System / Q000187:drug effects; D002986:Clinical Trials as Topic; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D010525:Peripheral Nerves / Q000187:drug effects; D010919:Placebos; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D010919:Placebos; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil