Monoamine transporter

Monoamine transporters are structures in nerve-cell membranes that function as neurotransmitter transporters transferring monoamine neurotransmitters in or out of cells.

Types

There are several different monoamine transporters:

• The dopamine transporter, DAT.
• The norepinephrine transporter, NET.
• The serotonin transporter, SERT.
• The less-specific monoamine transporter, PMAT.

DAT, NET and SERT are related^[vague] to each other, and each consists of a structure of 12 transmembrane helices.

Pharmacology

Many drugs, such as antidepressants and psychoactives affect the monoamine transporters (MATs).

Modern antidepressants typically work by enhancing serotonergic, noradrenergic or dopaminergic neurotransmission by binding to the corresponding transporter, and thereby inhibiting neurotransmitter reuptake and raising active levels in the synapse. Examples include fluoxetine, a selective serotonin reuptake inhibitor; reboxetine, a norepinephrine reuptake inhibitor and bupropion, which inhibits both the norepinephrine and dopamine transporter.

The euphoric and addictive properties of amphetamine, methamphetamine and cocaine are thought to come from their potent DAT-blocking activity.

Triple MAT agents (aka SNDRI's oder TRI)

16e

• PRC200-SS
• JNJ-7925476
• (+)-trans-5c^[1]
• nocaine-modafinil hybrids such as 16e.^[2]

• tropanes with "remote phenyl binding"^[3]

See also

• Glutamate transporter
• Vesicular monoamine transporter

References

1. ^ He R, Kurome T, Giberson KM, Johnson KM, Kozikowski AP (2005). "Further structure-activity relationship studies of piperidine-based monoamine transporter inhibitors: effects of piperidine ring stereochemistry on potency. Identification of norepinephrine transporter selective ligands and broad-spectrum transporter inhibitors". J. Med. Chem. 48 (25): 7970–9. doi:10.1021/jm050694s. PMID 16335921. 
2. ^ Zhou J, He R, Johnson KM, Ye Y, Kozikowski AP. Piperidine-based nocaine/modafinil hybrid ligands as highly potent monoamine transporter inhibitors: efficient drug discovery by rational lead hybridization. Journal of Medicinal Chemistry. 2004 Nov 18;47(24):5821-4. PMID 15537337
3. ^ Blough BE, Keverline KI, Nie Z, Navarro H, Kuhar MJ, Carroll FI (2002). "Synthesis and transporter binding properties of 3beta-[4'-(phenylalkyl, -phenylalkenyl, and -phenylalkynyl)phenyl]tropane-2beta-carboxylic acid methyl esters: evidence of a remote phenyl binding domain on the dopamine transporter". J. Med. Chem. 45 (18): 4029–37. doi:10.1021/jm020098n. PMID 12190324. 

G.E. Torres, R.R. Gainetdinov and M.G. Caron (2003). "Plasma membrane monoamine transporters: structure, regulation and function". Nat. Rev. Neurosci. 4 (1): 13–25. doi:10.1038/nrn1008. PMID 12511858.  (Review)

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