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Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

Sitte HH, Freissmuth M - Trends Pharmacol. Sci. (2014)

Bottom Line: Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse.Currently, a surge of new psychoactive substances occurs on a global scale.A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University Vienna, Waehringerstrasse 13A, 1090 Vienna, Austria; Center for Addiction Research and Science (AddRess), Medical University Vienna, Waehringerstrasse 13A, 1090 Vienna, Austria. Electronic address: harald.sitte@meduniwien.ac.at.

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Chemical structures of amphetamines.
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Figure 3: Chemical structures of amphetamines.

Mentions: The chemical definition by Biel and Bopp [3] posits the presence of (i) an unsubstituted phenyl ring, (ii) a two-carbon side chain between the phenyl ring and a nitrogen, (iii) an α-methyl group, and (iv) a primary amino group in a compound to qualify as an amphetamine (Figure I). Panel (A) illustrates this rule. Panel (B) shows the trace amine phenethylamine which is produced in higher organisms, while panels (C,D) show the structures of the plant alkaloids ephedrine and cathinone. Panels (E–I) show the structural diversity in amphetamines, which either conform to (E) or violate the chemical definition of Biel and Bopp rule (F–I). Accordingly, amphetamines are a diverse group of compounds that target the transporters for monoamine neurotransmitters, but do not engage their cognate receptors [75]. Moreover, the individual structural differences between the different amphetamines highlight the specificity between monoamine transporters, for example the SERT over DAT selectivity of pCA and fenfluramine [1,76], or the DAT-preference of D-amphetamine [75]. However, amphetamines also bind to nonmonoamine transporter targets such as adrenergic receptors [1] or trace amine receptors [77]. These receptors form complexes with transporters [78]; trace amine-associated receptor (TAR) agonists (including amphetamines) inhibit uptake [79,80]. These observations point to a possible role of TARs in the treatment of amphetamine addiction. The compound structures are reproduced from the PubChem database.


Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

Sitte HH, Freissmuth M - Trends Pharmacol. Sci. (2014)

Chemical structures of amphetamines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4502921&req=5

Figure 3: Chemical structures of amphetamines.
Mentions: The chemical definition by Biel and Bopp [3] posits the presence of (i) an unsubstituted phenyl ring, (ii) a two-carbon side chain between the phenyl ring and a nitrogen, (iii) an α-methyl group, and (iv) a primary amino group in a compound to qualify as an amphetamine (Figure I). Panel (A) illustrates this rule. Panel (B) shows the trace amine phenethylamine which is produced in higher organisms, while panels (C,D) show the structures of the plant alkaloids ephedrine and cathinone. Panels (E–I) show the structural diversity in amphetamines, which either conform to (E) or violate the chemical definition of Biel and Bopp rule (F–I). Accordingly, amphetamines are a diverse group of compounds that target the transporters for monoamine neurotransmitters, but do not engage their cognate receptors [75]. Moreover, the individual structural differences between the different amphetamines highlight the specificity between monoamine transporters, for example the SERT over DAT selectivity of pCA and fenfluramine [1,76], or the DAT-preference of D-amphetamine [75]. However, amphetamines also bind to nonmonoamine transporter targets such as adrenergic receptors [1] or trace amine receptors [77]. These receptors form complexes with transporters [78]; trace amine-associated receptor (TAR) agonists (including amphetamines) inhibit uptake [79,80]. These observations point to a possible role of TARs in the treatment of amphetamine addiction. The compound structures are reproduced from the PubChem database.

Bottom Line: Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse.Currently, a surge of new psychoactive substances occurs on a global scale.A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University Vienna, Waehringerstrasse 13A, 1090 Vienna, Austria; Center for Addiction Research and Science (AddRess), Medical University Vienna, Waehringerstrasse 13A, 1090 Vienna, Austria. Electronic address: harald.sitte@meduniwien.ac.at.

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Related in: MedlinePlus