1. Opiate Receptor Pharmacology
Donald R. Wesson, MD

2. Opiate Receptors and effect of Agonist
Mu1 (μ1)
analgesia, euphoria
Mu2 (μ2)
constipation, respiratory depression
Kappa
spinal analgesia, dysphoria
Delta
unknown

3. Schematic of Mu Opiate Receptor
Comparison of the amino acid sequences of the cloned mouse deta and kapa and rat mu receptor. The blue indicated common amino acid sequences. G protein couple receptors.
Source: Goodman and Gillman 9th ed, p. 526

4. 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)

5. Effect of Common Opiates at Mu Receptor
Heroin, morphine, methadone
Buprenorphine
Naltrexone
Nalmefene
Agonists
Partial Agonist
Antagonist

7. 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

8. 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)