NMDA Receptor Antagonists
Receptors other than the GABAA receptors are affected by chronic alcohol consumption. The NMDA receptor is a glutamatergic excitatory receptor that is thought to be involved in the development of alcohol dependence.64-66 Ethanol is an NMDA receptor antagonist, and chronic antagonism of the NMDA receptor results in upregulation of neurotransmission.67 Like the GABAA receptor, this increase in neurotransmission is likely related to alteration of receptor subunits rather than an increase in the absolute number of NMDA receptors.68 In the acute alcohol withdrawal state, there is uninhibited NMDA receptor activity, resulting in CNS hyperstimulation. This scenario offers a biologically plausible approach to combating the underlying pathophysiology of CNS hyperexcitability seen in alcohol withdrawal.
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