Macrolides in roles beyond antibiotic therapy

Abstract

Erythromycin and other macrolides with a closely related structure are widely used antibiotics. Side-effects related to administration of such drugs are mostly gastrointestinal. The direct effect of erythromycin on gastrointestinal motility was studied; it was found to have a stimulatory effect proximally, on stomach and duodenal motility, with an apparent distal inhibition. Gastric emptying was accelerated by erythromycin via an antroduodenal coordination mechanism, an effect that has proved to be beneficial in surgical and medical conditions in which gastroparesis is a problem. Erythromycin is now used experimentally and clinically; it has been found to accelerate gastric as well as gallbladder emptying and to have an effect on the oesophagus. Analogues of erythromycin have been developed that have potent gastrointestinal activity but little or no antibacterial potential. Macrolides modulate the antibacterial action of neutrophils, with some action on the oxidative burst. Finally, two new macrolide immunosuppressants have been developed that compare favourably with traditional drugs.