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Pathway Description
Methadone NMDA Antagonism Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-07-11
Last Updated: 2023-11-27
Methadone is an opioid analgesic indicated for the management of severe pain not responsive to alternate treatments. It is also used in detoxification of opioid addiction. Methadone is primarily an agonist for mu opioid receptors and an antagonist of N-methyl-d-aspartate(NMDA) receptors. It has also been found tobe an agonist of kappa- and delta-opioid receptors, and an antagonist of serotonin and norepinephrine uptake receptors.
Methadone is diffused across the blood-brain barrier into the central nervous system after being rapidly absorbed through the intestine. It antagonizes the NMDA receptors on the post synaptic nociceptive neurons in the central nervous system. This causes hyperpolarization of the neuron and prevents depolarization. This causes an analgesic effect in a major excitatory pain pathway. The inhibition of NMDA possibly explains methadone's improved analgesic efficacy and reduced opioid tolerance.
References
Methadone NMDA Antagonism Pathway References
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