Frontiers in Cardiovascular Drug Discovery

Volume: 4

Adenosine Receptors and Drug Discovery in the Cardiovascular System

Author(s): Maan T. Khayat, Ahmad Hanif, Werner J. Geldenhuys and Mohammed A. Nayeem

Pp: 16-64 (49)

DOI: 10.2174/9781681083995118040004

* (Excluding Mailing and Handling)

Abstract

The signaling nucleoside adenosine is produced intra- and extracellularly under physiologic and, more importantly, under pathologic conditions. Adenosine modulates cellular functions involved in injury, metabolic derangement, energy perturbations, and inflammation. The biologic effects of adenosine are mediated by four adenosine receptor (AR) subtypes of the G-protein coupled receptors (GPCRs) family: A1AR, A2AAR, A2BAR and A3AR. In the cardiovascular (CV) system, adenosine and its receptors are intricately involved in the regulation of myocardial contraction, heart rate, sympathetic control, conductivity, vascular tone, cardiac and vascular growth, inflammation, injury and apoptosis. As such, the modulation of the adenosinergic system has therapeutic potential for cardiovascular diseases (CVDs) such as metabolic disorders, atherosclerosis, hypertrophy, ischemic heart diseases, and heart failure. Nevertheless, despite the many years of investigation and experimentation only a few drugs targeting the adenosinergic system were developed and actually have reached clinical application. This chapter outlines the unique role adenosine plays in the CV system in physiology, pathology, and potentially therapeutic pharmacology. It also presents an updated review of the different adenosine receptors ligands, and their clinical potential in different CVDs.


Keywords: 4′-oxonucleosides, 4′-selenonucleoside, Adenosine, Adenosine receptors, Allosteric modulator, Atherosclerosis, Binding affinity, Capadenoson, Cardiac hypertrophy, Cardiovascular system, CGS 21680, Heart failure, Ischemic heart disease, Istradefylline, Metabolic disorders, Receptor dimerization, Receptor desensitization, Regadenoson, Rolofylline, Tecadenoson, Xanthine.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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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 <= 316202228 and j.to_ip >=316202228 )) and ((j.from_date <= 1740515480 and j.to_date >= 1740515480 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12029) 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 <= 316202228 and j.to_ip >=316202228 )) and ((j.from_date <= 1740515480 and j.to_date >= 1740515480 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12029) 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 <= 316202228 and j.to_ip >=316202228 )) and ((j.from_date <= 1740515480 and j.to_date >= 1740515480 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12029)
      970μsalphaeurekaselec_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` = 2437 and `b`.`banner_from_date` <= 1740515480 and `b`.`banner_to_date` >= 1740515480 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2437
      • 3: 1740515480
      • 4: 1740515480
      • 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='ca13571763ccd4cce02acc7d52e5499c'
      250μsalphaeurekaselec_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\Keywords
    21Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        0AVHbFoCXYImSSQQk8lewcew3lQVFi2SuKISEMTV
        uc_cart_id
        ca13571763ccd4cce02acc7d52e5499c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12029" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12029
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
        0 of 0
        array:5 [ "_token" => "0AVHbFoCXYImSSQQk8lewcew3lQVFi2SuKISEMTV" "uc_cart_id" => "ca13571763ccd4cce02acc7d52e5499c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12029" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:31:20GET/chapter/120291121923