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Review
. 2020 Jan 23:10:1590.
doi: 10.3389/fphar.2019.01590. eCollection 2019.

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Miguel Reyes-Parada  1   2 , Patricio Iturriaga-Vasquez  3 , Bruce K Cassels  4
Affiliations
Review

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Miguel Reyes-Parada et al. Front Pharmacol. .

Abstract

Amphetamine and its derivatives exhibit a wide range of pharmacological activities, including psychostimulant, hallucinogenic, entactogenic, anorectic, or antidepressant effects. The mechanisms of action underlying these effects are usually related to the ability of the different amphetamines to interact with diverse monoamine transporters or receptors. Moreover, many of these compounds are also potent and selective monoamine oxidase inhibitors. In the present work, we review how structural modifications on the aromatic ring, the amino group and/or the aliphatic side chain of the parent scaffold, modulate the enzyme inhibitory properties of hundreds of amphetamine derivatives. Furthermore, we discuss how monoamine oxidase inhibition might influence the pharmacology of these compounds.

Keywords: amphetamine derivatives; dopamine transporter; monoamine oxidase; monoamine oxidase-A; norepinephrine transporter; serotonin syndrome; serotonin transporter.

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Figures

Figure 1
Figure 1
Chemical structures of some AMPH derivatives.
Figure 2
Figure 2
Binding modes of (A) 5-HT and (B) MTA to MAO-A (PDB: 2BXS). (C) Superimposed structures of 5-HT and MTA docked into the active site of MAO-A. (D) Superimposed binding sites of MAO-A (green residues) and MAO-B (orange residues) with MTA already docked into the active site of MAO-A; the “wrapper” around MTA represents the solvent accessible surface area (SASA). In all cases, for the sake of clarity, only the most relevant residues are shown. Docking conditions were as in Fierro et al., 2007.
Figure 3
Figure 3
Chemical structures and MAO parameters of some phenethylamine/AMPH derivative pairs. a Youdim et al., 2006. b Scorza et al., 1997. c Reyes-Parada et al., 1994b. d Reyes-Parada et al., 1994a.
Figure 4
Figure 4
Chemical structures and MAO-A IC50 of some α-substituted AMPH derivatives. a Santillo, 2014. b Hurtado-Guzmán et al., 2003.
Figure 5
Figure 5
Chemical structures and MAO-A IC50 of some enantiomerically pure AMPH derivatives. a Ask et al., 1982b. b Fierro et al., 2007. c Hurtado-Guzmán et al., 2003.
Figure 6
Figure 6
Chemical structures and MAO-A IC50 of some β-keto substituted AMPH derivatives. a Scorza et al., 1997. b Osorio-Olivares et al., 2004. c Hurtado-Guzmán et al., 2003.
Figure 7
Figure 7
Chemical structures and MAO-A IC50 of some N-substituted AMPH derivatives. a Hurtado-Guzmán et al., 2003. b Vilches-Herrera et al., 2009.
Figure 8
Figure 8
Chemical structures and MAO-A IC50 of some p-substituted AMPH derivatives. a Hurtado-Guzmán et al., 2003. b Scorza et al., 1997. c Reyes-Parada et al., 1994a. d Osorio-Olivares et al., 2004. e Vallejos et al., 2002. f Fuller et al., 1975.
Figure 9
Figure 9
Chemical structures and MAO-A IC50 of some p-alkylthio AMPH derivatives. a Scorza et al., 1997. b Fierro et al., 2007. cVilches-Herrera et al., 2016.
Figure 10
Figure 10
Chemical structures and MAO-A IC50 of some p-methoxy AMPH derivatives. IC50 values are from Scorza et al., 1997. NE, No effect.
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