Possible Interaction: Ethanol and Ifenprodil

“The GIRK currents induced by ethanol were also attenuated in the presence of ifenprodil.”

“Consistent with earlier reports, ifenprodil selectively inhibited responses mediated by recombinant receptors containing the NMDAR2B subunit at concentrations up to 10 microM. EtOH also inhibited the function of recombinant NMDA receptors expressed in HEK 293 cells.”

“Inhibition by EtOH was decreased in magnitude in the presence of 10 microM ifenprodil in 2- to 3-wk-old cortical neurons, but not in 1-wk-old neurons.”

“ EtOH inhibition of neuronal NMDA receptors expressed in some brain areas has been reported to be occluded by the presence of ifenprodil or similar compounds suggesting that the NTD may be important in regulating the EtOH sensitivity of NMDA receptors.”

“…),ifenprodil (0.5 mg/kg) as antagonists of NMDAR, and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), 7-nitroindazole (7-NI, …,3-a]quinoxalin-1-one (ODQ) (20 mg/kg) a nitric oxide/cyclic-guanosine monophosphate (NO-cGMP) inhibitor, with a subeffective dose of ethanol (….”

“ Ifenprodil , a GluN2B polyamine site antagonist, significantly reduced toxicity from EtOH and CORT (0.1 μM) co-exposure during EWD.”

“In the CA1 region of rat hippocampal slices, ethanol partially inhibited N-methyl-d-aspartate receptor-… concentrations up to 180 mM. The block of synaptic N-methyl-d-aspartate receptors by 60mM ethanol occluded … microM ifenprodil , an agent that has relative selectivity for … receptors expressing NR1 and NR2B subunits.”

“ Ifenprodil also occluded the ethanol effect, suggesting that NR2B subunit-containing receptors may be involved.”

“Comparison of the potencies of ethanol and ifenprodil in inhibiting NMDA-evoked [3H]neurotransmitter release revealed an excellent correlation (r = 0.96; P<0.001).”

“In view of the ability of ifenprodil to interact with ethanol at NMDA receptors, which are important sites of action of ethanol, ifenprodil may be assumed to influence neuronal effects of ethanol in vivo.”

“It is concluded that ethanol predominantly inhibits NMDA receptors containing a high proportion of the NMDAR2B subunit (as reflected by high sensitivity to ifenprodil ), i.e. the NMDA receptors involved in stimulation of noradrenaline, 5-hydroxytryptamine and GABA release.”

“However, ifenprodil reduced the inhibition by ethanol of NMDA-gated currents from neurons isolated from the lateral septum without affecting neurons from the substantia nigra.”

“In contrast, although ifenprodil also reduced the stimulant effects of ethanol , the antagonist did not alter expression of sensitization.”