CNS-Transporters as Drug Targets

Nerve cells are widely distributed in the mammalians, particularly in the central nervous system (CNS). Nerve cells synthesize, store, and eventually release their neurotransmitters into the synaptic cleft between the presynaptic and the postsyn-aptic neuron. Nature is conservative, hence evolution has provided specialized membrane proteins to allow the organism to reuse the neurotransmitters. These membrane transport proteins strictly control the concentration of neurotransmitters in the synaptic cleft. 

The neurotransmitter transporters are responsible for terminating or modulating the action of neurotransmitters released from the presynaptic neuron. The transport of neurotransmitters takes place against a concentration gradient thus, transport is coupled to the downhill transport of Na. Furthermore, the SLCl family requires K transport, while SLC6 requires a cotransport of Cl . 

The structures of thousands of proteins have been resolved through X-ray crystallography. Membrane proteins represent a special class in this respect, as they are not easily crystallizable. Thus, ligand-based approaches for drug design (e.g.. 

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