Mechanism of Action

A great deal of attention has been focused on a class of proteins termed the ligand-gated ion channels as being important to the mechanism of action of alcohol. These integral membrane proteins function as gates or pores that allow the passage of certain ions into and out of neurons upon binding of the appropriate neurotransmitter. This flux of ions largely determines the degree of neuronal activity. Two distinct types of ligand-gated ion channels are particularly sensitive to concentrations of alcohol that produce intoxication and sedation. These are the a-aminobutyric acid (GABA) chloride ionophore and the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor. The GABA-chloride ion channel reduces neuronal activity by hyperpolarizing the neurons, while activation of the NMDA receptor causes neuronal depolarization or excitation. Alcohol has been shown to increase chloride flux through the GABAA receptor and reduce calcium flux through the NMDA receptor. These actions result in powerful suppression of nerve cell activity, which is consistent with the depressant actions of alcohol in the brain.

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