Synaptic membrane structure as a determinant of CNS drug actions and interactions

The purpose of this communication is to review the progress in determining the relationships between synaptic membrane structure and mechanisms of drug action. As far as possible, the focus of the discussion will be on CNS synaptic membrane constituents. However, occasionally it will be necessary to draw on information from peripheral neurons, neural cell cultures, and, in some cases, from non-neuronal tissues. Finally, the emphasis of this review will be on the synaptic membrane lipids. Given the difficulty in isolating, purifying and assigning a function to synaptic membrane proteins, it seems likely that our most productive focus in determining structural-functional relationships will be on the membrane lipids. The data reviewed here illustrate the variety of roles synaptic membrane lipids can play in the mechanisms of neurotransmitter and drug action. In some cases, the lipids may be part of the receptor complex and directly participate in the physiological or pharmacological effect. In other cases, the lipids may serve a more regulatory or modulatory role. However, the overall importance of the lipid effects cannot be denied and future studies will only serve to expand upon and confirm this importance.