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Background Of the three opioid receptors, μ (MOP), δ (DOP) and (KOP), the MOP type is the most involved in the action of opioids in the gut. Experimental studies on models of intestinal inflammation and inflammatory bowel disease (IBD) support an anti-inflammatory role of peripheral MOP receptors in the gut, besides their involvement in pain control (analgesia) and gastrointestinal motility (anti-diarrheal effects). Research focuses increasingly on exploring the therapeutic potential of peripheral MOP receptors aiming for identification of peripheral ligands as improved treatment for debilitating conditions associated with bowel functions. One strategy to increase peripheral selectivity includes chemical modifications that enhance hydrophilicity [1,2]. Our work in the field of peripherally acting opioids has led to a series of opioids with zwitterionic moieties (i.e. amino acid residues) attached to the C-6 position of 14-O-methyloxymorphone, which may represent novel therapeutic molecules for IBD. These 14-alkoxymorphinans were pharmacologically and immunologically characterized.

Biological, pharmacological and immunological activities of novel 6-amino-acid-substituted 14-alkoxy-N-methylmorphinans