Opioid Receptor Mechanism of Action
Opioids bind primarily to the mu (μ) opioid receptor to elicit their therapeutic and adverse effects. 1, 2
Primary Receptor Target
The mu opioid receptor (MOR) is the principal receptor responsible for opioid analgesia, with opioids also binding to delta (δ) and kappa (κ) receptors to a lesser extent. 2
Opioids exert their pharmacologic effects by binding to specific opioid receptors present throughout the central nervous system and peripheral tissues. 1
Binding to the μ receptor subtype is primarily responsible for the analgesic effect that makes opioids clinically useful for pain management. 1
Receptor Distribution and Clinical Effects
Mu opioid receptors are highly expressed in brain regions that regulate pain perception including the periaqueductal gray, thalamus, cingulate cortex, and insula. 2
MORs are also located in brain regions associated with reward (ventral tegmental area, nucleus accumbens), which explains the addictive potential of opioids. 2
The brainstem respiratory center (pre-Bötzinger complex) contains mu receptors, accounting for the life-threatening complication of opioid-induced respiratory depression. 2
Gastrointestinal Effects Through Multiple Receptor Types
Opioid-induced constipation occurs primarily via activation of enteric μ-receptors, which results in increased tonic non-propulsive contractions in the small and large intestine, increased colonic fluid absorption, and stool desiccation. 1
Opioids also exert gastrointestinal effects via κ-receptors in the stomach and small intestine, and μ-receptors located in the small intestine and proximal colon. 1
Critical Clinical Implications
Mixed agonist-antagonist opioid analgesics (pentazocine, nalbuphine, butorphanol) must be avoided in patients on maintenance opioid therapy because they will displace the maintenance opioid from the μ receptor, precipitating acute opioid withdrawal. 1
The high affinity of buprenorphine for the μ receptor complicates acute pain treatment, as it risks displacement of or competition with full opioid agonist analgesics when administered concurrently. 1
Tolerance to opioid analgesic effects develops faster than tolerance to respiratory depression, increasing overdose risk even in chronic users. 2