Straight‐chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits

The effects of n ‐alcohols (methanol to 1‐decanol) on kainate‐activated AMPA receptor subunit GluR1 and GluR3 ion currents were studied in Xenopus oocytes using the two‐electrode voltage‐clamp recording technique. For short‐chain alcohols from methanol to 1‐hexanol, potency for inhibition of GluR1 and GluR3 receptor‐mediated current increased in proportion to the chain length or hydrophobicity of the alcohol. The IC 50 values of these alcohols for GluR1 were: methanol, 702 m M ; ethanol, 170 m M ; 1‐propanol, 69 m M ; 1‐butanol, 20 m M ; 1‐pentanol, 17 m M ; and 1‐hexanol, 10 m M . For GluR3, IC 50 values were: methanol, 712 m M ; ethanol, 238 m M ; 1‐propanol, 50 m M ; 1‐butanol, 32 m M ; 1‐pentanol, 13 m M ; and 1‐hexanol, 7 m M . For long‐chain alcohols, 1‐heptanol was less potent than 1‐hexanol (estimated IC 50 : 19 m M for GluR1 and 18 m M for GluR3), 1‐octanol had little effect only on GluR3, and 1‐nonanol and 1‐decanol did not significantly inhibit both GluR1 and GluR3 responses. The observations indicate that straight‐chain n ‐alcohols exhibit a cutoff in their potency for inhibition of the function of non‐NMDA glutamate receptor subunits, GluR1 and GluR3. The cutoff in potency of n ‐alcohols for inhibition of non‐NMDA glutamate receptor function is consistent with the interpretation that alcohols affect the function of these receptor‐channels by interacting with an alcohol binding site of specific dimensions on the receptor protein.British Journal of Pharmacology (2001) 133 , 651–658; doi: 10.1038/sj.bjp.0704112