Dextromethorphan is a drug most commonly used as a cough suppressant present in many over the counter cough medication. Coughing is activated in the cough center of the brain, which is located in the medulla oblongata, What receptors are targeted by Dextromethorphan is known, but the exact mechanism is unknown. Its metabolite dextrorphan acts in a very similar way. Dextromethorphan inhibits NMDA receptors, nicotinic acetylcholine receptors, and sigma-1 receptors. Dextromethorphan binds to neuronal acetylcholine receptors, specifically thought to be the α3/β4 nicotinic receptors. Dextromethorphan is an antagonist to nAch α3/β4 receptors which means that when Dextromethorphan binds to nicotinic acetylcholine receptor α3/β4, acetylcholine is unable to bind to it, preventing the channel from opening and allowing sodium into the neuron. With Sodium unable to enter the neuron, the neuron cannot depolarize which stops the signal or makes it much more difficult to get a signal through the neurons. It is unknown where the acetylcholine receptors might be located as they could be present anywhere along the pathway between the lungs and the cough center of the brain. The pathway travels along the vagus nerve where nicotinic acetylcholine receptors are present in the dorsal vagal nucleus.The dorsal vagal nucleus is in the medulla part of the vagus nerve, but specifics of how this receptor effects cough or specifically where are unknown. Sigma-1 receptors have a high affinity for binding to synthetic compounds such as Dextromethorphan. Sigma-1 receptors do not seem to have any role in preventing coughing. They are present in the endoplasmic reticulum of central nervous system neurons, where they regulate calcium and potassium, but the reason for that is not well understood. The side-effects Dextromethorphan causes because of its affinity for Sigma-1 receptors are not much better understand than the effects it has on coughing.

Dextromethorphan Nicotinic Acetylcholine Antagonism Pathway References