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.
Highlights
Since its first description as “Phenisopropylamin” more than a century ago (Edeleano, 1887), amphetamine (1-phenylpropan-2-amine, phenylisopropylamine, amfetamine, alphamethylphenethylamine; AMPH; Figure 1) has received considerable attention due to its multiple psychotropic effects, first noted in the early 1930s (Prinzmetal and Bloomberg, 1935)
competitive monoamine oxidase (MAO)-A inhibitory properties are found in many AMPH derivatives
AMPH is indicated for the treatment of attention deficit hyperactivity disorder
Summary
Since its first description as “Phenisopropylamin” more than a century ago (Edeleano, 1887), amphetamine (1-phenylpropan-2-amine, phenylisopropylamine, amfetamine, alphamethylphenethylamine; AMPH; Figure 1) has received considerable attention due to its multiple psychotropic effects, first noted in the early 1930s (Prinzmetal and Bloomberg, 1935). Osorio-Olivares et al (2004) reported that cathinone is almost completely devoid of activity as a MAOI, whereas some derivatives with alkylthio or alkoxy groups at the para position of the aromatic ring have IC50 values in the low micromolar range (Table 3) These results indicate that b-keto substitution of AMPH may lead to a decrease in MAOI-A potency (Figure 6). Some of these compounds showed an interesting MAO-B inhibiting activity (Table 3), which suggests that selectivity can be effectively modulated by side-chain substituents.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
