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Pathway Description
Methadone Action Pathway
Homo sapiens
Drug Action Pathway
Methadone exerts its analgesic by acting on the mu-opioid receptor of sensory neurons. Binding to the mu-opioid receptor activates associated G(i) proteins. These subsequently act to inhibit adenylate cyclase, reducing the level of intracellular cAMP. G(i) also activates potassium channels and inactivates calcium channels causing the neuron to hyperpolarize. The end result is decreased nerve conduction and reduced neurotransmitter release, which blocks the perception of pain signals. Methadone further acts as an antagonist at the NMDA receptor, reducting calcium influx and neuronal excitability.
References
Methadone Pathway References
Fredheim OM, Moksnes K, Borchgrevink PC, Kaasa S, Dale O: Clinical pharmacology of methadone for pain. Acta Anaesthesiol Scand. 2008 Aug;52(7):879-89. doi: 10.1111/j.1399-6576.2008.01597.x. Epub 2008 Mar 7.
Pubmed: 18331375
Opioids. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved October 25, 2009.
Neuron Function References
Lovinger DM: Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol. Alcohol Res Health. 2008;31(3):196-214.
Pubmed: 23584863
Kress GJ, Mennerick S: Action potential initiation and propagation: upstream influences on neurotransmission. Neuroscience. 2009 Jan 12;158(1):211-22. doi: 10.1016/j.neuroscience.2008.03.021. Epub 2008 Mar 19.
Pubmed: 18472347
Platkiewicz J, Brette R: A threshold equation for action potential initiation. PLoS Comput Biol. 2010 Jul 8;6(7):e1000850. doi: 10.1371/journal.pcbi.1000850.
Pubmed: 20628619
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