Ethanol inhibits NMDA-activated ion currents in hippocampal neurons. The study shows that ethanol (EtOH) reduces the amplitude of NMDA-activated currents in voltage-clamped hippocampal neurons, with inhibition increasing in a concentration-dependent manner from 5 to 50 mM. At 50 mM EtOH, the NMDA-activated current was reduced by 61%, while the inhibition of kainate and quisqualate-activated currents was much less (18% and 15%, respectively). This suggests that EtOH specifically inhibits NMDA receptor activity, which may contribute to the neural and cognitive impairments associated with intoxication. The study also examined the effects of various alcohols on NMDA-activated currents. Methanol, 1-butanol, and isopentanol inhibited the NMDA-activated current similarly to 50 mM EtOH. The potency of these alcohols for inhibiting NMDA currents correlated with their hydrophobicity and intoxicating potency. The IC50 values for inhibition of NMDA currents by these alcohols were related to their intoxicating potency, indicating that the mechanism of alcohol action may involve inhibition of NMDA receptor activity. The study further suggests that EtOH inhibits NMDA-activated currents in a concentration range that corresponds to the range of EtOH concentrations that produce intoxication in humans. This inhibition may contribute to the cognitive and motor impairments associated with ethanol intoxication. However, the study also notes that EtOH does not significantly affect voltage-activated Na+ or Ca2+ currents, suggesting that its effects on NMDA currents are not nonspecific. The study concludes that inhibition of NMDA receptor activity by EtOH may play a role in the neural and cognitive impairments associated with ethanol intoxication. The findings suggest that the mechanism of alcohol action involves specific interactions with NMDA receptors, which are involved in excitatory neural phenomena, neural plasticity, and cognitive function. The results highlight the importance of understanding the molecular mechanisms underlying alcohol's effects on the nervous system.Ethanol inhibits NMDA-activated ion currents in hippocampal neurons. The study shows that ethanol (EtOH) reduces the amplitude of NMDA-activated currents in voltage-clamped hippocampal neurons, with inhibition increasing in a concentration-dependent manner from 5 to 50 mM. At 50 mM EtOH, the NMDA-activated current was reduced by 61%, while the inhibition of kainate and quisqualate-activated currents was much less (18% and 15%, respectively). This suggests that EtOH specifically inhibits NMDA receptor activity, which may contribute to the neural and cognitive impairments associated with intoxication. The study also examined the effects of various alcohols on NMDA-activated currents. Methanol, 1-butanol, and isopentanol inhibited the NMDA-activated current similarly to 50 mM EtOH. The potency of these alcohols for inhibiting NMDA currents correlated with their hydrophobicity and intoxicating potency. The IC50 values for inhibition of NMDA currents by these alcohols were related to their intoxicating potency, indicating that the mechanism of alcohol action may involve inhibition of NMDA receptor activity. The study further suggests that EtOH inhibits NMDA-activated currents in a concentration range that corresponds to the range of EtOH concentrations that produce intoxication in humans. This inhibition may contribute to the cognitive and motor impairments associated with ethanol intoxication. However, the study also notes that EtOH does not significantly affect voltage-activated Na+ or Ca2+ currents, suggesting that its effects on NMDA currents are not nonspecific. The study concludes that inhibition of NMDA receptor activity by EtOH may play a role in the neural and cognitive impairments associated with ethanol intoxication. The findings suggest that the mechanism of alcohol action involves specific interactions with NMDA receptors, which are involved in excitatory neural phenomena, neural plasticity, and cognitive function. The results highlight the importance of understanding the molecular mechanisms underlying alcohol's effects on the nervous system.