The serotonin transporter: a primary
target for antidepressant drugs

by
Schloss P, Williams DC
Biochemistry Department,
University of Dublin, Trinity College, Ireland.
schlossp@mail.tcd.ie
J Psychopharmacol 1998; 12(2):115-21


ABSTRACT

The serotoninergic system is known to modulate mood, emotion, sleep and appetite and thus is implicated in the control of numerous behavioural and physiological functions. Decreased serotoninergic neurotransmission has been proposed to play a key role in the aetiology of depression. The concentration of synaptic serotonin is controlled directly by its reuptake into the pre-synaptic terminal and, thus, drugs blocking serotonin transport have been successfully used for the treatment of depression. In addition to tricyclic antidepressants (TCAs; e.g. imipramine) which also block noradrenaline reuptake, highly specific serotonin reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine have been developed, which are increasingly prescribed for depressed patients. The mode of action of these antidepressant drugs on their direct target, the serotonin transport protein, and possible regulatory mechanisms with respect to long-term alleviation of depression, although having been investigated both neurobiologically and clinically over the last years, are not yet understood. The cloning of the cDNA encoding the serotonin transporter has allowed a more precise characterization of this protein at the molecular level. This will show how antidepressants act at this target, thereby affecting the biochemical, pharmacological and electrophysiological properties of the serotoninergic system and give an introduction of how they might exert their therapeutic effect. This review gives an overview of the recent developments in this field, discusses mechanisms of antidepressant action on this target, and also possible interactions with other components of serotoninergic neurotransmission.
TCAs
SSRIs
Suicide
Serotonin
Dopamine
Melancholia
Noradrenaline
SSRI spectrum
SSRI mechanisms
Future anxiolytics
Serotonin research
MDMA neurotoxicity
21C antidepressants
The serotonin receptors
Serotonin and psychedelics
SNaRIs, NaSSAs, and NaRIs
Serotonin and romantic lovers
The monoamine theory of depression
Fluoxetine (Prozac): 10th Anniversary
Serotonin and the genetics of depression
Serotonin reuptake inhibitors v enhancers
Antidepressant efficacy and 'publication bias'
Dopaminergic and noradrenergic antidepressants
Are SSRI antidepressants little better than placebos?
Dopamine, depression and dopaminergic antidepressants

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