Neurotransmitter transporters and their impact on the development of psychopharmacology
by
Iversen L
Department of Pharmacology,
University of Oxford,
Mansfield Road,
Oxford
OX1 3QT, UK.
Br J Pharmacol. 2006 Jan;147 Suppl 1:S82-8.


ABSTRACT

The synaptic actions of most neurotransmitters are inactivated by reuptake into the nerve terminals from which they are released, or by uptake into adjacent cells. A family of more than 20 transporter proteins is involved. In addition to the plasma membrane transporters, vesicular transporters in the membranes of neurotransmitter storage vesicles are responsible for maintaining vesicle stores and facilitating exocytotic neurotransmitter release. The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline-selective and serotonin-selective reuptake inhibitors are effective against major depression and a range of other psychiatric illnesses. As the newer drugs are safer in overdose than the first-generation tricyclic antidepressants, their use has greatly expanded. The dopamine transporter (DAT) is a key target for amphetamine and methylphenidate, used in the treatment of attention deficit hyperactivity disorder. Psychostimulant drugs of abuse (amphetamines and cocaine) also target DAT. The amino-acid neurotransmitters are inactivated by other families of neurotransmitter transporters, mainly located on astrocytes and other non-neural cells. Although there are many different transporters involved (four for GABA; two for glycine/D-serine; five for L-glutamate), pharmacology is less well developed in this area. So far, only one new amino-acid transporter-related drug has become available: the GABA uptake inhibitor tiagabine as a novel antiepileptic agent.
MAOIs
Opioids
Reward
Cocaine
Cannabis
Dopamine
Future opioids
Dopaminergics
NMDA antagonists
The monoamine hypothesis
Drink, drugs and asceticism
The neural basis of addiction
Antidepressants and monoamine transporters


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