Benzhydrocodone is a benzylic prodrug of hydrocodone.It was developed to reduce parenteral bioavailability of the active metabolite as a deterrent of abuse.It was first approved by the FDA in February 2018 in combination with acetaminophen. Benzhydrocodone is metabolized in the liver by CYP2D6 or CYP3A4 into hydrocodone. Hydrocodone is transported to the dorsal horn of the spinal cord where it inhibits mu opioid receptors. Hydrocodone binds to mu opioid receptors on presynaptic neuron membranes, stimulating the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal cord. By decreasing neurotransmitter action there is less pain transmittance into the spinal cord. This leads to less pain perception.

Benzhydrocodone Opioid Agonist Pathway References