New Developments in Macrolides: Structures and Antibacterial and Prokinetic Activities

• Published in: Advances in Pharmacology Vol. 28; pp. 307 - 343
• Main Authors: Lartey, P.A., Nellans, H.N., Tanaka, S.K.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Inc 1994; Elsevier Science & Technology
• Subjects: Animals; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Cytochrome P-450 Enzyme System - drug effects; Drug Resistance, Microbial; ENVIRONMENTAL ENGINEERING & TECHNOLOGY; Erythromycin - pharmacology; Humans; Neurosciences; Pharmacology; Protein Synthesis Inhibitors - pharmacology; Receptors, Gastrointestinal Hormone - drug effects; Receptors, Neuropeptide - drug effects; Structure-Activity Relationship
• ISBN: 012032928X; 9780120329281
• ISSN: 1054-3589; 1557-8925
• DOI: 10.1016/S1054-3589(08)60499-8

This chapter focuses on advances in the discovery and introduction of novel derivatives of erythromycin with improved pharmacokinetics, antibacterial spectrum, and reduced side effects. Advances have also been made toward understanding pharmacological actions of erythromycin that are unrelated to the mechanism of its antibacterial activity. Erythromycin has proven itself as a safe and useful antibiotic. Years of synthetic modifications have led to the introduction of new derivatives with improvements in its antibacterial spectrum, pharmacokinetics, and side effects. As the use of these new agents increases, a corresponding increase in bacterial resistance is inevitable. Future directions may well include a quest for analogs or strategies to overcome resistance. Undoubtedly, one of the more intriguing advances, analogous to the morphine and encephalin relationship, is the discovery that macrolide derivatives are highly potent agonists for receptors of the endogenous peptide, motilin. The smooth muscle-stimulating effects of motilin are exceptionally well mimicked by these compounds.