Receptors: Act as agonists at opioid receptors (μ, δ, κ), which are Gi protein-coupled receptors. The μ-receptor is the most important for analgesia and the primary mediator of most clinical and adverse effects.
Cellular Effect: Activation leads to closing of presynaptic voltage-gated Ca2+ channels (↓ neurotransmitter release, e.g., substance P, ACh, NE, glutamate) and opening of postsynaptic K+ channels (→ hyperpolarization, ↓ neuronal excitability).
Overall Effect: Produces analgesia, sedation, and euphoria.
Classification
Full agonists
Morphine, heroin
Methadone
Meperidine
Codeine
Fentanyl
Partial agonist: buprenorphine
Mixed agonist/antagonists
Butorphanol
Nalbuphine
Pentazocine
Full antagonists
Naloxone
Naltrexone
Methylnaltrexone
Adverse effects
Constipation (not affected by tolerance, most common and persistent opioid side effect.)
