Receptor and blood-brain barrier characterization of opioid peptides in drug research & early development

The opioid receptors (ORs) are known to be distributed widely in the central nervous system (CNS) and in peripheral sensory and autonomic nerves. Activation of ORs by endogenous and exogenous ligands results in a multitude of physiological functions and behaviors, e.g. pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, and many more [1]. Due to this widespread pharmacological profile of ORs, opioid peptides are becoming key players in the pharmaceutical industry, more specifically in research and development of pain modulating agents. Among the opioid receptor subtypes, the μ-opioid receptor subtype is the main target due to its essential contribution to control pain (i.e. narcotic analgesics used in clinic are all agonists of the μ-opioid receptor subtype) [2]. For analgesics to target ORs in the CNS and exert medical activity, opioid peptides should penetrate the blood–brain barrier (BBB), with limited efflux behavior, have a favorable receptor-subtype selectivity and sufficient metabolic stability.