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Synthesis and psychobiological evaluation of modafinil analogs in mice

BACKGROUND AND THE PURPOSE OF THE STUDY: Modafinil, a novel wake-promoting agent with low potential for abuse and dependence, has a reliable structure to find some novel derivatives with better activity and lower potential for abuse and risk of dependency. This study was designed to evaluate psychob...

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Autores principales: Lari, Arezou, Karimi, Isaac, Adibi, Hadi, Aliabadi, Alireza, Firoozpour, Loghman, Foroumadi, Alireza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897940/
https://www.ncbi.nlm.nih.gov/pubmed/24355111
http://dx.doi.org/10.1186/2008-2231-21-67
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author Lari, Arezou
Karimi, Isaac
Adibi, Hadi
Aliabadi, Alireza
Firoozpour, Loghman
Foroumadi, Alireza
author_facet Lari, Arezou
Karimi, Isaac
Adibi, Hadi
Aliabadi, Alireza
Firoozpour, Loghman
Foroumadi, Alireza
author_sort Lari, Arezou
collection PubMed
description BACKGROUND AND THE PURPOSE OF THE STUDY: Modafinil, a novel wake-promoting agent with low potential for abuse and dependence, has a reliable structure to find some novel derivatives with better activity and lower potential for abuse and risk of dependency. This study was designed to evaluate psychobiological activity of some novel N-aryl modafinil derivatives. METHODS: Seven novel N-aryl modafinil derivatives were synthesized through three reactions: a) preparation of benzhydrylsulfanyl acetic acid through reaction of benzhydrol with thioglycolic acid, b) formation of desired amide by adding the substituted aniline to activated acid with EDC (1-ethyl-3-(3-dimethyl amino propyl) carbodiimide). This reaction was catalyzed by HOBt (N- hydroxylbenzotriazole), and c) oxidation of sulfur to sulfoxide group with H(2)O(2). Then, their psychobiological effect on the performance of male albino mice were compared to that of modafinil as following: wakefulness by determining the effects of derivatives on phenobarbital-induced loss of the righting reflex (LOPR); exploratory activity by measuring activity in the open field test (OFT); depression by measuring immobility time (IT) during forced swimming test (FST) and the anxiogenic and anxiolytic like effects by using elevated plus-maze test (EPM). All tests were videotaped and analyzed for the frequency and duration of the behaviors during the procedures. CONCLUSIONS: 2-(Benzhydrylsulfonyl)-N-(4-chlorophenyl)acetamide (4c) showed comparable result in LOPR test. However, all analogs were found to be stimulant except 2-(benzhydrylsulfinyl)-N-phenylacetamide (4a). Also 4c led the most exploratory activity in mice among derivatives. FST results showed that 4a had the longest IT while modafinil, 2-(benzhydrylsulfinyl)-N-(3-chlorophenyl) acetamide (4b) and 2-(benzhydrylsulfinyl)-N-(4-ethylphenyl) acetamide (4d) had the shortest IT. In EPM, all derivatives showed anxiogenic-like behavior since they decreased open arms time and open arms entries and simultaneously increased close arms time.
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spelling pubmed-38979402014-01-23 Synthesis and psychobiological evaluation of modafinil analogs in mice Lari, Arezou Karimi, Isaac Adibi, Hadi Aliabadi, Alireza Firoozpour, Loghman Foroumadi, Alireza Daru Research Article BACKGROUND AND THE PURPOSE OF THE STUDY: Modafinil, a novel wake-promoting agent with low potential for abuse and dependence, has a reliable structure to find some novel derivatives with better activity and lower potential for abuse and risk of dependency. This study was designed to evaluate psychobiological activity of some novel N-aryl modafinil derivatives. METHODS: Seven novel N-aryl modafinil derivatives were synthesized through three reactions: a) preparation of benzhydrylsulfanyl acetic acid through reaction of benzhydrol with thioglycolic acid, b) formation of desired amide by adding the substituted aniline to activated acid with EDC (1-ethyl-3-(3-dimethyl amino propyl) carbodiimide). This reaction was catalyzed by HOBt (N- hydroxylbenzotriazole), and c) oxidation of sulfur to sulfoxide group with H(2)O(2). Then, their psychobiological effect on the performance of male albino mice were compared to that of modafinil as following: wakefulness by determining the effects of derivatives on phenobarbital-induced loss of the righting reflex (LOPR); exploratory activity by measuring activity in the open field test (OFT); depression by measuring immobility time (IT) during forced swimming test (FST) and the anxiogenic and anxiolytic like effects by using elevated plus-maze test (EPM). All tests were videotaped and analyzed for the frequency and duration of the behaviors during the procedures. CONCLUSIONS: 2-(Benzhydrylsulfonyl)-N-(4-chlorophenyl)acetamide (4c) showed comparable result in LOPR test. However, all analogs were found to be stimulant except 2-(benzhydrylsulfinyl)-N-phenylacetamide (4a). Also 4c led the most exploratory activity in mice among derivatives. FST results showed that 4a had the longest IT while modafinil, 2-(benzhydrylsulfinyl)-N-(3-chlorophenyl) acetamide (4b) and 2-(benzhydrylsulfinyl)-N-(4-ethylphenyl) acetamide (4d) had the shortest IT. In EPM, all derivatives showed anxiogenic-like behavior since they decreased open arms time and open arms entries and simultaneously increased close arms time. BioMed Central 2013-12-19 /pmc/articles/PMC3897940/ /pubmed/24355111 http://dx.doi.org/10.1186/2008-2231-21-67 Text en Copyright © 2013 Lari et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lari, Arezou
Karimi, Isaac
Adibi, Hadi
Aliabadi, Alireza
Firoozpour, Loghman
Foroumadi, Alireza
Synthesis and psychobiological evaluation of modafinil analogs in mice
title Synthesis and psychobiological evaluation of modafinil analogs in mice
title_full Synthesis and psychobiological evaluation of modafinil analogs in mice
title_fullStr Synthesis and psychobiological evaluation of modafinil analogs in mice
title_full_unstemmed Synthesis and psychobiological evaluation of modafinil analogs in mice
title_short Synthesis and psychobiological evaluation of modafinil analogs in mice
title_sort synthesis and psychobiological evaluation of modafinil analogs in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897940/
https://www.ncbi.nlm.nih.gov/pubmed/24355111
http://dx.doi.org/10.1186/2008-2231-21-67
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