Levacetylmethadol, also known as Levomethadyl acetate, Levacetylmethadol is a narcotic analgesic with a long onset and duration of action. It was withdrawn from the European Union due to its high risk of QT interval prolongation. Its production also ceased in the United States. Levacetylmethadol is an agonist of mu-opioid receptors. It is also an antagonist of neuronal acetylcholine receptors with unknown pharmacological effects. Levacetylmethadol 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.

Levacetylmethadol Opioid Agonist Pathway References