Novel opioid antagonists for opioid-induced bowel dysfunction

Introduction: Adverse effects frequently limit the therapeutic benefits of opioid analgesics. Gastrointestinal adverse effects are common, burdensome, and can compromise the quality of life. It is estimated that up to 81% of patients still report constipation despite regular use of laxatives. Thus, the development of opioid antagonists that selectively target receptors in the gut without affecting central analgesia has provided new perspectives on the treatment of opioid-induced gastrointestinal adverse effects.

Areas covered: In this paper, we review the pathophysiology, prevalence, and burden of opioid-induced bowel dysfunction (OBD). In addition, this study aims to provide a better understanding of the mechanism of action and reviews the efficacy, safety and the latest research on novel opioid antagonists for OBD.

Expert opinion: Two strategies effectively relieve OBD without interfering with centrally mediated analgesia: the administration of opioid antagonists with limited systemic absorption and peripherally acting mu-opioid receptor antagonists (PAMORA) that selectively target mu-receptors in the gastrointestinal tract. Methylnaltrexone and alvimopan are two recently marketed PAMORA and provide a new mechanism-based approach for the treatment of opioid-induced gastrointestinal dysfunction. However, its use in clinical practice is limited by various reasons such as its relatively low response rates and higher costs. Nevertheless, at least four new oral PAMORA (NKTR-118, TD-1211, ADL-7445, and ADL-5945) are under clinical development, further expanding the possibilities for a new paradigm for OBD management.