The Sound of Evolution
Fentanyl
Mechanism of action:
Fentanyl is an opioid and a synthetic μ-opioid receptor agonist. Fentanyl activates μ-opioid receptors in the central and peripheral nervous systems. Through Gi/o proteins, it inhibits adenylyl cyclase and reduces cAMP production, which in turn suppresses presynaptic voltage-gated Ca²⁺ channels, preventing calcium ions from entering the cell and decreasing the release of pain-related neurotransmitters such as glutamate and substance P, thereby reducing pain signal transmission. In addition, it activates postsynaptic potassium channels, causing neuronal membrane hyperpolarization and reducing the likelihood of neuronal firing.
Reference(s):
1. Van Bever WF et al. (1974). Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide. J Med Chem.
2. Taylor DR et al. (2007). Fentanyl buccal tablet: rapid relief from breakthrough pain. Expert Opin Pharmacother.