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Opiate Receptor Pharmacology
Donald R. Wesson, MD
Opiate Receptors and effect of Agonist
Mu1 (μ1) analgesia, euphoria
Mu2 (μ2) constipation, respiratory depression
Kappa spinal analgesia, dysphoria
Delta unknown
Schematic of Mu Opiate Receptor
Source: Goodman and Gillman 9th ed, p. 526
Receptor Binding at Mu receptor
Agonist
Partial Agonist
Antagonists
Morphine-like effect (e.g., heroin, weak binding except for Fentanyl)
Weak morphine-like effects with strong receptor affinity (e.g., buprenorphine)
No effect in absence of an opiate or opiate dependence (e.g., naltrexone)
Effect of Common Opiates at Mu Receptor
• Heroin, morphine, methadone
• Buprenorphine
• Naltrexone• Nalmefene
Agonists
Partial Agonist
Antagonist
Partial vs Full Opiate Mu Agonist
Dose of Opiate
OpiateEffect
death
Full Agonist(e.g., methadone)
Partial Agonist(e.g. buprenorphine)
Buprenorphine Pharmacology
• Partial agonist at mu receptor
• High affinity for mu receptor
• Can displace full opiate agonist such as heroin or methadone– Displacement of heroin or methadone by
buprenorphine can produce opiate withdrawal symptoms
Buprenorphine Pharmacology
• Antagonist at kappa receptor
• Poor bio-availability taken orally (extensive first pass metabolism)
• Much more bio-available from sublingual mucosa (Peak 2-3 hours following sublingual dose)