Peripheral mu-opioid, kappa-opioid, and delta-opioid receptors (MOR/KOR/DOR (Peripheral))

Peripheral opioid receptors consist of the mu (MOR), kappa (KOR), and delta (DOR) subtypes located in tissues outside the central nervous system, such as the gastrointestinal tract, peripheral sensory neurons, and immune cells (Stein & Lang, 2009; StatPearls, 2023). These receptors are members of the G protein-coupled receptor (GPCR) family and primarily function to modulate pain transmission and regulate autonomic processes like bowel motility (Galligan & Sternini, 2017). In clinical practice, these receptors are targeted to treat conditions where central opioid effects are undesirable, such as opioid-induced constipation (OIC) or uremic pruritus (NIDDK, 2021). For example, peripheral mu-opioid receptor antagonists (PAMORAs) like naloxegol are used to reverse the constipating effects of opioids in the gut without compromising central pain relief (FDA, 2014). Additionally, peripheral kappa-opioid receptor agonists like difelikefalin are employed to alleviate chronic itch by acting on peripheral nerve endings (Fishbane et al., 2020). By focusing on peripheral localization, these therapeutic strategies aim to minimize common opioid-related risks like respiratory depression, sedation, and physical dependence (Waldhoer et al., 2004). The development of drugs for these targets often involves chemical modifications, such as PEGylation or quaternary ammonium structures, to restrict their activity to the periphery (Cami-Kobeci et al., 2011). Overall, peripheral opioid receptors represent a crucial interface for managing the side effects of opioid therapy and treating localized sensory disorders.

Other names

Peripheral opioid receptorsPeripheral mu-opioid receptorPeripheral kappa-opioid receptorPeripheral delta-opioid receptorOPRM1OPRK1OPRD1Extracellular opioid receptors

Selective agonism or antagonism of opioid receptors located in peripheral tissues (e.g., enteric nervous system, peripheral sensory neurons) to modulate physiological functions while minimizing blood-brain barrier penetration (Stein & Lang, 2009; Galligan & Sternini, 2017).