Neurotransmitter transporters: fruitful targets for CNS drug discovery.
More than 20 members have been identified in the neurotransmitter transporter family. These include the cell surface re-uptake mechanisms for monoamine and amino acid neurotransmitters and vesicular transporter mechanisms involved in neurotransmitter storage. The norepinephrine and serotonin re-uptake transporters are key targets for antidepressant drugs. Clinically effective antidepressants include those with selectivity for either NE or serotonin uptake, and compounds with mixed actions. The dopamine transporter plays a key role in mediating the actions of cocaine and the amphetamines and in conferring selectivity on dopamine neurotoxins. The only clinically used compound to come so far from research on amino acid transporters is the antiepileptic drug tiagabine, a GABA uptake inhibitor.
Iversen
L
L
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
D000928:Antidepressive Agents / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy*; D050483:Dopamine Plasma Membrane Transport Proteins; D015195:Drug Design; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters
D000928:Antidepressive Agents; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters