Biogenic amine transporters:
regulation in flux

by
Blakely RD, Bauman AL
Department of Pharmacology,
Center for Molecular Neuroscience,
Vanderbilt University School of Medicine,
Nashville,
37232-6420, USA.
randy.blakely@mcmail.vanderbilt.edu
Curr Opin Neurobiol 2000 Jun; 10(3): 328-336


ABSTRACT

Following vesicular release, the biogenic amine neurotransmitters dopamine, norepinephrine and serotonin are actively cleared from extracellular spaces by presynaptic transporters. These transporters interact with multiple psychoactive agents including cocaine, amphetamines and antidepressants. Recent findings indicate that amine reuptake is likely to be a tightly regulated component of synaptic plasticity rather than a constitutive determinant of transmitter clearance. Protein kinase C activation and transporter phosphorylation have been linked to regulatory protein trafficking, and both phosphorylation and trafficking may be influenced by transporter ligands. Recognition that transmitters, antagonists and second messengers can modify the intrinsic activity, surface expression or protein levels of amine transporters raises new questions about the fundamental nature of drug actions in vivo. The theory that dysregulation of transporters may contribute to disease states is supported by the recent discovery that a coding mutation in the human norepinephrine transporter contributes to orthostatic intolerance.
SSRIs
NARIs
5-HT2
Serotonin
Anhedonia
Noradrenaline
Antidepressants
Major depression
Tyrosine hydroxylase
Tryptophan hydroxylase
Noradrenaline depletion
Catecholamine depletion
An individualised approach
New ways to treat depression
Monoamines and 'novel' antidepressants
The monoamine hypothesis of depression
The catecholamine hypothesis of depression
Pharmacogenomics and new antidepressants
Antidepressants and monoamine transporters


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