Inhibition of monoamine oxidase (MAO) by α-ethylphenethylamine and N,α-diethylphenethylamine, two compounds related to dietary supplements

Santillo, Michael F.

doi:10.1016/j.fct.2014.10.009

Cited by 15 publications

(7 citation statements)

References 38 publications

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“…d Reyes-Parada et al, 1994a FIGURE 4 | Chemical structures and MAO-A IC 50 of some a-substituted AMPH derivatives. a Santillo, 2014. b Hurtado-Guzmán et al, 2003 MAOI-A, much more potent than AMPH ( Table 5).…”

Section: Aromatic Ring Substitutionmentioning

confidence: 99%

“…methamphetamine, NMM TA, P MMA, and MDM A respectively-have about one-third the inhibitory potency of their corresponding primary amine congeners (Scorza et al, 1997;Hurtado-Guzmán et al, 2003;Matsumoto et al, 2014;Santillo, 2014;Tables 1, 2, 4). In addition, enlargement of the amine substituent to N-ethyl, N-n-propyl, or N-allyl seems to cause a further decrease in MAO-A affinity, correlated with the length of the substituent (Kilpatrick et al, 2001;Hurtado-Guzmán et al, 2003;Santillo, 2014; Figure 7). Even larger substituents such as N-benzyl can lead to a complete loss of MAOI properties (Vilches-Herrera et al, 2009).…”

Section: N-substitutionmentioning

confidence: 99%

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Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

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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.

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Section: Aromatic Ring Substitutionmentioning

confidence: 99%

Section: N-substitutionmentioning

confidence: 99%

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

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“…It is hypothesized that, once in the monoaminergic terminals, METH acts on the monoamine storage vesicles and depletes them of neurotransmitters by reversing the vesicular monoamine transporter 2 (VMAT2) and collapsing the pH gradient across the vesicular membrane (Sulzer and Rayport, 1990;Sulzer et al, 1995;Brown et al, 2000). In addition, METH inhibits monoamine metabolism via inhibition of monoamine oxidase (Suzuki et al, 1980;Egashira and Yamanaka, 1993;Santillo, 2014). The net result of these actions is an increase in intracellular levels of cytoplasmic DA and other monoamines.…”

Section: Pharmacology Of Methmentioning

confidence: 99%

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment

Moszczynska

Callan

2017

J Pharmacol Exp Ther

112

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Understanding the relationship between the molecular mechanisms underlying neurotoxicity of high-dose methamphetamine (METH) and related clinical manifestations is imperative for providing more effective treatments for human METH users. This article provides an overview of clinical manifestations of METH neurotoxicity to the central nervous system and neurobiology underlying the consequences of administration of neurotoxic METH doses, and discusses implications of METH neurotoxicity for treatment of human abusers of the drug.

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“…Among the 27 test compounds studied, several are known to exist in dietary supplements, whereas others are structural analogs that were evaluated since they could emerge in future products. Some of the most potent CYP2D6 inhibitors in the current study have been reported to exist in dietary supplements, including DMAA, β‐methylphenethylamine, higenamine, N ,β‐dimethylphenethylamine, and N ,α‐diethylphenethylamine . N , N ‐diethylphenethylamine was previously listed on a dietary supplement product label, but the product actually contained the isomer N ,α‐diethylphenethylamine .…”

Section: Resultsmentioning

confidence: 79%

“…Some of the most potent CYP2D6 inhibitors in the current study have been reported to exist in dietary supplements, including DMAA, [1] β-methylphenethylamine, [2] higenamine, [3] N,βdimethylphenethylamine, [14] and N,α-diethylphenethylamine. [15,16] N,N-diethylphenethylamine was previously listed on a dietary supplement product label, but the product actually contained the isomer N,α-diethylphenethylamine. [15] Additionally, several of the weaker CYP2D6 inhibitors are also found on dietary supplement labels (US National Institutes of Health Dietary Supplement Label Database; http://www.dsld.nlm.nih.gov) such as β-phenethylamine, N,N-dimethylphenethylamine, halostachine, octopamine, and hordenine.…”

Section: Resultsmentioning

confidence: 99%

Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements

Liu

Santillo

2015

Drug Testing and Analysis

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A number of dietary supplements used for weight loss and athletic performance enhancement have been recently shown to contain a variety of stimulants, for which there is a lack of pharmacological and toxicological information. One concern for these emerging compounds is their potential to inhibit metabolic enzymes in the liver such as cytochromes P450 (CYP), which can lead to unexpected interactions among dietary supplements, drugs, and other xenobiotics. In this study, inhibition of human recombinant CYP2D6 and CYP3A4 by 27 amine stimulants associated with dietary supplements and their analogs was evaluated by luminescence assays. The strongest CYP2D6 inhibitors were coclaurine (IC50 = 0.14 ± 0.01 μM) and N-benzylphenethylamine (IC50 = 0.7 ± 0.2 μM), followed by several other relatively strong inhibitors (IC50 , 2-12 μM) including β-methylphenethylamine, N,β-dimethylphenethylamine (phenpromethamine), 1,3-dimethylamylamine (DMAA), N,α-diethylphenethylamine, higenamine (norcoclaurine) and N,N-diethylphenethylamine. Only nine compounds inhibited CYP3A4 by 20-55% at 100 μM. Results of this study illustrate that several amine stimulants associated with dietary supplements inhibit CYP2D6 and CYP3A4 in vitro, and these compounds may participate in adverse drug-dietary supplement interactions in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

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Inhibition of monoamine oxidase (MAO) by α-ethylphenethylamine and N,α-diethylphenethylamine, two compounds related to dietary supplements

Cited by 15 publications

References 38 publications

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment

Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements

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