Editing Monoamine transporter (section)

==Associated disorders and treatments==
Monoamine transporters are believed to be factors in several neurological conditions due to their role in reuptake of the monoamines dopamine, noradrenaline, and serotonin. These conditions include [[ADHD]], [[Major depressive disorder|depression]], [[drug abuse]], [[Parkinson's disease]], [[schizophrenia]], and [[Tourette's syndrome]].  Evidence supporting this belief includes that monoamine transporters, DAT, NET, and SERT, are important target sites for therapeutic drugs used in the treatment of mood disorders.  Several drugs are used to treat disease symptoms by blocking monoamine transporters, which results in an increase in extracellular monoamines.<ref name= Sitte>{{cite book|title=Handbook of Neurochemistry and Molecular Neurobiology: Neural Membranes and Transport|year=2007|publisher=Springer Reference|isbn=978-0-387-30347-5|author=H.H. Sitte|edition=3rd|author2=M. Freissmuth|editor=Abel Lajta|chapter=17: Monoamine transporters in the brain: Structure and Function}}</ref>  In addition, the levels of monoamine transporters have been shown to be altered in many of these psychiatric and neurological conditions.  Finally, [[Polymorphism (biology)|polymorphic]] variations in monoamine transporter genes have been proposed to be associated with conditions such as ADHD and depression.<ref name=Torres/>

===Attention deficit hyperactivity disorder===
It has been observed that the hyperactivity, inattention, and impulsivity in ADHD is related to abnormal DAT function and regulation.  [[Dopaminergic]] hypofunction in the frontal cortex and [[basal ganglia]] is a neurobiological feature observed in ADHD.<ref name=Fone/>  [[Psychostimulants]] that potently inhibit DAT, such as [[methylphenidate]] and [[amphetamine]], are efficacious in treating ADHD.  Methylphenidate (Ritalin) inhibits both DAT and NET, which results in an increase in extracellular dopamine and norepinephrine that can readily bind postsynaptic cells.  Methylphenidate targets DAT as a [[Reuptake inhibitor|non-selective reuptake inhibitor]].<ref name=rama/>   Methylphenidate is not an inhibitor of SERT.<ref name=Fone>{{cite journal|doi=10.1016/j.coph.2004.10.001|last=Fone|first=Kevin|author2=David J Nutt|title=Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder|journal=Current Opinion in Pharmacology|date=February 2005|volume=5|issue=1|pages=87–93|pmid=15661631}}</ref>

===Depression===
It has been observed that the pathology of depression involves dysfunction of monoamine neurotransmitter circuits in the CNS, particularly of serotonin and norepinephrine.  [[Selective serotonin reuptake inhibitors]] (SSRIs) are the most widely used antidepressant and include [[fluoxetine]] (Prozac), [[citalopram]] (Celexa), and [[fluvoxamine]] (Luvox).  These drugs inhibit the reuptake of serotonin from the extracellular space into the synaptic terminal by selectively inhibiting SERT.  It has been recently observed that serotonin, norepinephrine, and dopamine may all be involved in depression.  Therefore, drugs such as [[venlafaxine]] and [[paroxetine]] are being used as effective antidepressants that selectively inhibit both SERT and NET.<ref name=Nemeroff>{{cite journal|last=Nemeroff|first=Charles B.|author2=Michael J. Owens|title=Treatment of mood disorders|doi=10.1038/nn943 |pmid=12403988|journal=Nature Neuroscience|date=October 2002|pages=1068–1070|volume=5|s2cid=35112132}}</ref>  The [[tricyclic antidepressant]] [[desipramine]] is an antidepressant drug that is a relatively selective inhibitor of NE uptake.  Studies of inhibition of NET correlate with antidepressant activity.<ref name=Reith>{{cite book|title=Neurotransmitter Transporters|year=1997|publisher=Humana Press Inc.|isbn=0-89603-372-4|author=Maarten E. A. Reith|author-link=Role of Axonal and Somatodendritic Monoamine Transporters in Action of Uptake Blockers|author2=Nian-Hang Chen|editor=Maarten E. A. Reith}}</ref>

===Schizophrenia===
NET regulation is linked to altered dopamine transmission and schizophrenia-like behaviors.  [[Nisoxetine]] is a NET inhibitor and reverses some schizophrenia-linked behavior. NET activities regulate NE as well as DA equilibrium.  In addition, for normal DA clearance a functional DAT is necessary which suggests that DAT dysfunction may contribute to schizophrenia.<ref name=rama/>