Is the picrotoxinin binding site at the GABA synapse a site of action for barbiturates

摘要: Abstract The molecular mechanisms involved in barbiturate action have yet to be elucidated. Recent neurophysiological studies suggest a possible involvement of GABA synaptic events action. Our indicate that the racemic barbiturates inhibit binding antagonist, ( 3 H) α-dihydropicrotoxinin (DHP), rat brain membrane. Several lines evidence DHP is associated with receptor-ionophores, but distinct from receptor sites. Thus, depressant like secobarbital (IC 50 =5 μM), hexobarbital = 12 μM) and pentobarbital micromolar range. interaction between appears competitive. also displaced by convulsant stereoisomers barbiturates. displacement curves obtained deviate Law Mass Action, suggesting heterogenity Stereoisomers 1-methyl-5-phenyl-propylbarbituric acid (MPPB), which produce opposite pharmacological effects, inhibited 10-fold difference. These findings are consistent may related their modulation mediated inhibitory transmission. possibility modulate linked chloride ionophores discussed.