Frontiers in Clinical Drug Research - CNS and Neurological Disorders

Volume: 12

Drug Repurposing in CNS and Clinical Trials: Recent Achievements and Perspectives Focusing on Epilepsy and Related Comorbidities

Author(s): Gabriela Machado Parreira, Antonio Carlos Pinheiro de Oliveira, Leonardo de Oliveira Guarnieri* and Rafael Pinto Vieira * .

Pp: 171-202 (32)

DOI: 10.2174/9789815179842124120007

* (Excluding Mailing and Handling)

Abstract

Central Nervous System (CNS) disorders are a massive burden on the global health system, including a broad range of clinical conditions, such as epilepsies, depression, dementia, multiple sclerosis, and Parkinson’s disease. Permanent efforts are being made to find early, non-invasive, and effective diagnostic methods, as well as efficient and safe drug-based treatments for CNS conditions. Nevertheless, many patients displaying these clinical conditions still face the lack of an effective pharmacotherapy to cure the diseases or at least to properly control the progression of symptoms. Currently, epilepsies present an estimated prevalence of 0.5%–1% worldwide, and around 30% of the patients remain refractory to the available drug treatment. The comorbidities that affect epileptic patients, such as cognitive impairment and depression, are major public health challenges. This scenario highlights the urgent need for approving new therapeutic tools for CNS diseases. A successful development process of a new compound presenting therapeutic potential can range up to 20 years and cost hundreds of millions of US dollars, from the initial characterization of the in vitro chemical and biological properties until clinical trials. Additionally, drug development has a low success rate in the case of CNS conditions. In this context, drug repurposing (or drug repositioning, DR) is an alternative way to reduce the cost and accelerate the process of a drug-based treatment approach since it identifies a novel clinical application for an existing compound already approved for a distinct indication. In the present chapter, we aim to describe recent outcomes of DR aiming at CNS pathological conditions, especially discussing the recent clinical trials and their impacts on future endeavors in the search for the management of epilepsies and related comorbidities.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834423 and j.to_date >= 1739834423 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 21743) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834423 and j.to_date >= 1739834423 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 21743) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834423 and j.to_date >= 1739834423 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 21743)
      570μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3677 and `b`.`banner_from_date` <= 1739834423 and `b`.`banner_to_date` >= 1739834423 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.05msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3677
      • 3: 1739834423
      • 4: 1739834423
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='3fc77e0d3fb35b61954805199b61cf18'
      210μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        Mqt0Gfiw26zRx6oNfVpJ9kVRJroc1PVoT752HZ8s
        uc_cart_id
        3fc77e0d3fb35b61954805199b61cf18
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/21743" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/21743
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "_ga_9F3B5VV3T3=GS1.1.1739834410.1.0.1739834410.60.0.0; _ga=GA1.2.355363239.1739834411; _gid=GA1.2.1101351624.1739834414; _gat=1; wayfindertarget=eyJpdiI6Ik5scndDMFRYK0ZPVGx6VG5DVWFhUEE9PSIsInZhbHVlIjoiU212VHBJNzVzVHdxUzltbW85dTFYUzZIekttOVpZLzg5L2hUdUY1YjJCQT0iLCJtYWMiOiI2YmNkMjU2NDU1Zjc4MWYzM2IzN2IzZDc5NTA0NTg3MDc3ZDY0OGFiNGRhYThkZmZhY2YxN2YwMDcwOWQwMTQ1IiwidGFnIjoiIn0%3D_ga_9F3B5VV3T3=GS1.1.1739834410.1.0.1739834410.60.0.0; _ga=GA1.2.355363239.1739834411; _gid=GA1.2.1101351624.1739834414; _gat=1; wayfindertarget=eyJpdiI6Ik5scnd" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:5 [ "_ga_9F3B5VV3T3" => null "_ga" => null "_gid" => null "_gat" => null "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:20:23 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InZRTmRFb0V1d1JNekI1dnZwRnR6dkE9PSIsInZhbHVlIjoiS2I1SVNFMFQ3dzIybDhkaGNFaUlwMXk1cGlhSXVla3BGZGZlalBsZENaNm0vdGhDaFdtTkJRZENzSUE4RU5yNXZHVjYyWkpmSFFOVjY2L09RK2xCMzJBRUo3bE4zakZpNC91b1I2cFc1TG5VdEVGLzI3UW1rVWhqVnBwU2ZTNFUiLCJtYWMiOiIwNDZlMjBmZDAyMGQ0OWFlY2JiMDE2ZTM2OGRmNWNjZDFhMjRjNjM5MTViNjIxMWQ5NTU1Njg0MGE0MWJiNTgxIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:20:23 GMT; Max-Age=215999; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InZRTmRFb0V1d1JNekI1dnZwRnR6dkE9PSIsInZhbHVlIjoiS2I1SVNFMFQ3dzIybDhkaGNFaUlwMXk1cGlhSXVla3BGZGZlalBsZENaNm0vdGhDaFdtTkJRZENzSUE4RU5yNXZHVjYyW" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImJSWmsvQUhzY2tpdVkybE00R21ta2c9PSIsInZhbHVlIjoiL3NvSEdnVklyUFBrR0lsemc1NW14VGVaVDdHY0tESEsvU3QzbWFzOXlZNk5VYkZwYy9FRUtWdHV0Qm5OUUJBaVVaOThJTVBUZWNqdlBwcEhib0xSSVNwV1dRMUdINlMzRCtMdk1ERytQRTNPMisyOFB3UUcyTFZJWWJ4VlAxR2siLCJtYWMiOiI0NTJlNzMyYjM1Zjg4NzgyOWMzMDlmNTUwMWVlZDJjN2NmNmJjNWUzZGU2ZjYzNmRhNmRhOTQ1OTMyNGU2ZTEzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImJSWmsvQUhzY2tpdVkybE00R21ta2c9PSIsInZhbHVlIjoiL3NvSEdnVklyUFBrR0lsemc1NW14VGVaVDdHY0tESEsvU3QzbWFzOXlZNk5VYkZwYy9FRUtWdHV" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InZRTmRFb0V1d1JNekI1dnZwRnR6dkE9PSIsInZhbHVlIjoiS2I1SVNFMFQ3dzIybDhkaGNFaUlwMXk1cGlhSXVla3BGZGZlalBsZENaNm0vdGhDaFdtTkJRZENzSUE4RU5yNXZHVjYyWkpmSFFOVjY2L09RK2xCMzJBRUo3bE4zakZpNC91b1I2cFc1TG5VdEVGLzI3UW1rVWhqVnBwU2ZTNFUiLCJtYWMiOiIwNDZlMjBmZDAyMGQ0OWFlY2JiMDE2ZTM2OGRmNWNjZDFhMjRjNjM5MTViNjIxMWQ5NTU1Njg0MGE0MWJiNTgxIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:20:23 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InZRTmRFb0V1d1JNekI1dnZwRnR6dkE9PSIsInZhbHVlIjoiS2I1SVNFMFQ3dzIybDhkaGNFaUlwMXk1cGlhSXVla3BGZGZlalBsZENaNm0vdGhDaFdtTkJRZENzSUE4RU5yNXZHVjYyW" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImJSWmsvQUhzY2tpdVkybE00R21ta2c9PSIsInZhbHVlIjoiL3NvSEdnVklyUFBrR0lsemc1NW14VGVaVDdHY0tESEsvU3QzbWFzOXlZNk5VYkZwYy9FRUtWdHV0Qm5OUUJBaVVaOThJTVBUZWNqdlBwcEhib0xSSVNwV1dRMUdINlMzRCtMdk1ERytQRTNPMisyOFB3UUcyTFZJWWJ4VlAxR2siLCJtYWMiOiI0NTJlNzMyYjM1Zjg4NzgyOWMzMDlmNTUwMWVlZDJjN2NmNmJjNWUzZGU2ZjYzNmRhNmRhOTQ1OTMyNGU2ZTEzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImJSWmsvQUhzY2tpdVkybE00R21ta2c9PSIsInZhbHVlIjoiL3NvSEdnVklyUFBrR0lsemc1NW14VGVaVDdHY0tESEsvU3QzbWFzOXlZNk5VYkZwYy9FRUtWdHV" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "Mqt0Gfiw26zRx6oNfVpJ9kVRJroc1PVoT752HZ8s" "uc_cart_id" => "3fc77e0d3fb35b61954805199b61cf18" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/21743" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:20:23GET/chapter/21743112192