Daily doses of the anti-impotence drug sildenafil (Viagra) may reverse gastroparesis, a condition commonly associated with diabetes, a new study has found. Dr Christopher Ferris and colleagues at Johns Hopkins University, Baltimore, used mouse models of diabetes to find that defects in their gastric emptying were linked to failure of production of a common protein that can be supplanted by daily doses of sildenafil.
After studying diabetic mice with gastroparesis, the researchers found that these mice were unable to relax their pyloric muscles. This was probably respon-sible for their gastroparesis, the scientists reasoned. On pathological examination, the team then found that the pyloric muscles of these mice had a striking deficit in production of neuronal nitric oxide synthase. The team postulated that a shortage of neuronal nitric oxide synthase was responsible for the inability of the pyloric muscle to relax in the diabetic mice and therefore a shortage of the protein might also be a culprit in gastroparesis.
Human gastroparesis has long been linked to failure to control blood glucose, and the symptoms generally resolve with insulin treatment. In this case the researchers found that when they gave insulin to their diabetic mice, expression of neuronal nitric oxide synthase was restored and gastric function in the diabetic mice resolved. This suggested that the mice and humans might share a common mechanism for diabetic gastroparesis. The researchers' findings were published in the Journal of Clinical Investigation (2000:106:373-84).
Because sildenafil has been known to augment production of neuronal nitric oxide synthase, the team tried giving the drug to mice deficient in the protein to see if it would restore pyloric motility and found that the drug indeed restored gastric emptying. The researchers will begin human trials this autumn with sildenafil in people with diabetic gastroparesis. If these trials prove that the treatment is safe, larger human studies will follow. Gastroparesis affects half of all diabetic people and three quarters of those who have had diabetes for more than five years. Currently, no effective long term treatment is available in the United States.
Cisapride, the most commonly used treatment, was withdrawn from the market earlier this year after warnings that it could cause dangerous cardiac arrhythmias. The problem mainly involved QT prolongation that in rare cases led to problems such as ventricular fibrillation and, sometimes, complete heart block. Dr Ferris said that the new findings might have implications beyond the treatment of diabetic gastroparesis.
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