sorbinil and Pain

A considerable volume of animal pharmacologic data support the view that increased flux through the polyol pathway provides a unifying hypothesis for the major complications of diabetes. An extensive clinical program has been established to verify the extrapolation of the animal pharmacologic findings to man. Clinical data accumulated to date confirm the biochemical and electrophysiologic effects, and encouraging evidence of a drug effect in diabetic neuropathy and retinopathy has already been observed. In the large, controlled safety data base already available, the long-term clinical use of sorbinil is devoid of significant adverse effects in terms of both subjective side effects and laboratory parameters. The only clinically important adverse reaction reported to date has been a hypersensitivity reaction in the early weeks of therapy, which is similar to that seen with other hydantoins.

Topics: Aldehyde Reductase; Animals; Autonomic Nervous System Diseases; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Pain; Rats; Sorbitol; Sugar Alcohol Dehydrogenases

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.

Topics: Adult; Aged; Aldehyde Reductase; Autonomic Nervous System; Clinical Trials as Topic; Diabetic Neuropathies; Female; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Neural Conduction; Pain; Peripheral Nerves; Placebos; Sugar Alcohol Dehydrogenases

Topics: Aldehyde Reductase; Clinical Trials as Topic; Diabetic Neuropathies; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Pain; Sugar Alcohol Dehydrogenases