Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Elsevier Science full text link Elsevier Science Free PMC article
Full text links

Actions

Share

Review
.2021 Feb:56:13-21.
doi: 10.1016/j.coph.2020.07.007. Epub 2020 Sep 11.

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

Affiliations
Review

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

Gianluigi Tanda et al. Curr Opin Pharmacol.2021 Feb.

Abstract

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.

Published by Elsevier Ltd.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest: AHN and JJC are inventors on the licensed US patent E-073–2013/0-US-06 -NIH0072US2 in which JJC8–088 and JJC8–091 are disclosed. The NIH owns all rights to this patent. All other authors declare that they have no interests to disclose.

Figures

Figure 1:
Figure 1:. Effects of R-MOD and MOD analogs on DA dynamics in mice accumbens shell.
Representative FSCV color plots, redrawn from [20], demonstrating the effects of R-MOD and MOD analogs, or their vehicle, on the elicited DA peak, DAMAX and clearance rate of NAS DA from the electrode. The inset above each color plot represents the DA concentration vs time corresponding to the measurement on the color plot.
Figure 2:
Figure 2:. Evaluation of the effects of JJC8–088 and JJC8–091 on self-administration or on cocaine self-administration behavior.
A: JJC8–091, but not JJC8–088, significantly lowered the number of cocaine self-administration (infusions) under the PR reinforcement schedule.B: JJC8088, but not JJC8–091, substitution sustained stable self-administration in rats that previously self-administered cocaine.C: Naive rats self-administered JJC8–088 intravenously similarly to cocaine.D: Naive rats did not self-administer JJC8–091 during the initial 10 days of self-administration training. When JJC8–091 was replaced by cocaine, animals rapidly acquired self-administration behavior for cocaine. **p < 0.01, compared to vehicle. Redrawn from [27].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kariisa M, Scholl L, Wilson N, Seth P, Hoots B: Drug overdose deaths involving cocaine and psychostimulants with abuse potential—United States, 2003–2017. Morbidity and mortality weekly report 2019, 68:388. - PMC - PubMed
    1. Mereu M, Bonci A, Newman AH, Tanda G: The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders. Psychopharmacology (Berl) 2013, 229:415–434. - PMC - PubMed
    1. Kampman KM, Lynch KG, Pettinati HM, Spratt K, Wierzbicki MR, Dackis C, O’Brien CP: A double blind, placebo controlled trial of modafinil for the treatment of cocaine dependence without co-morbid alcohol dependence. Drug Alcohol Depend 2015, 155:105–110. - PMC - PubMed
    1. Hamid AA, Pettibone JR, Mabrouk OS, Hetrick VL, Schmidt R, Vander Weele CM, Kennedy RT, Aragona BJ, Berke JD: Mesolimbic dopamine signals the value of work. Nature neuroscience 2016, 19:117. - PMC - PubMed

    1. Salatino-Oliveira A, Rohde LA, Hutz MH: The dopamine transporter role in psychiatric phenotypes. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2018, 177:211–231.

      * This review article provides a brief update on preclinical and clinical studies on DAT researchincluding DAT structure and function, as well as its implications in brain disorders.

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp