Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder

[Display omitted] Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder....

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Published inCurrent opinion in pharmacology Vol. 56; pp. 13 - 21
Main Authors Tanda, Gianluigi, Hersey, Melinda, Hempel, Briana, Xi, Zheng-Xiong, Newman, Amy Hauck
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.02.2021
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Abstract [Display omitted] Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.
AbstractList [Display omitted] Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.
Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.
Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.
Author Hempel, Briana
Tanda, Gianluigi
Hersey, Melinda
Xi, Zheng-Xiong
Newman, Amy Hauck
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  givenname: Amy Hauck
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Snippet [Display omitted] Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil...
Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved...
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SubjectTerms Animals
Benzhydryl Compounds - therapeutic use
Central Nervous System Stimulants - adverse effects
Cocaine
Dopamine Uptake Inhibitors
Humans
Modafinil
Title Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder
URI https://www.clinicalkey.com/#!/content/1-s2.0-S147148922030045X
https://dx.doi.org/10.1016/j.coph.2020.07.007
https://www.ncbi.nlm.nih.gov/pubmed/32927246
https://www.proquest.com/docview/2442846687
https://pubmed.ncbi.nlm.nih.gov/PMC8247144
Volume 56
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