Reactome | SLC6A4 binds TCAs and SSRIs

SLC6A4 binds TCAs and SSRIs

Stable Identifier

R-HSA-9714415

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

Synonyms

SERT binds SLC6A4 inhibitors

ReviewStatus

5/5

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Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. They are named after their 3-ringed chemical structure. Imipramine is the prototypical TCA that was also the first to be marketed in 1957 for the treatment of various depressive states. Other TCAs include amitriptyline, clomipramine, dosulepin, doxepin, and trimipramine. The use of imipramine and other TCAs have decreased in recent decades due to the introduction of the selective serotonin reuptake inhibitors (SSRIs), which have fewer side effects. SSRIs are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and illnesses related to serotonin deficiencies. Marketed SSRIs include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline.

Both TCAs and SSRIs function by increasing the extracellular levesl of the neurotransmitter serotonin. They achieve this by limiting the reabsorption of serotonin into the presynaptic cell by blocking the sodium-dependent serotinin transporter (SERT), encoded by the SLC6A4 gene (Richelson 1991, Richelson 2001, Barker & Blakely 1996, Richelson 2003, Zhou et al. 2007, Wang et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
24121440	Structural basis for action by diverse antidepressants on biogenic amine transporters Ressler, R, Wang, H, Wang, KH, Penmatsa, A, Goehring, A, Gouaux, E	Nature	2013
1646793	Biological basis of depression and therapeutic relevance Richelson, E	J Clin Psychiatry	1991
11357798	Pharmacology of antidepressants Richelson, E	Mayo Clin Proc	2001
14552650	Interactions of antidepressants with neurotransmitter transporters and receptors and their clinical relevance Richelson, E	J Clin Psychiatry	2003
17690258	LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake Reith, ME, Karpowich, NK, Law, CJ, Zhen, J, Wang, DN, Zhou, Z, Goetz, RM	Science	2007
8863842	Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter Blakely, RD, Barker, EL	Mol Pharmacol	1996