Medicinal Chemistry for Pharmacy Students

Author(s): Ashok E. Philip, George DeMaagd and M. O. Faruk Khan

DOI: 10.2174/9789811454073120020010

Parkinson Disease and Antiparkinsonian Drugs

Pp: 321-377 (57)

Buy Chapters
  • * (Excluding Mailing and Handling)

Medicinal Chemistry for Pharmacy Students

Volume: 2

Parkinson Disease and Antiparkinsonian Drugs

Author(s): Ashok E. Philip, George DeMaagd and M. O. Faruk Khan

Pp: 321-377 (57)

DOI: 10.2174/9789811454073120020010

* (Excluding Mailing and Handling)

Abstract

This chapter is a comprehensive account of Parkinson's disease and the medicinal chemistry of antiparkinsonian drugs. It provides the mechanism of disease progression and drug action and detail structure-activity relationships of the antiparkinsonian drugs to give the knowledge base for pharmacists. After a study of this chapter, students will be able to:

• Discuss the epidemiology and etiology of Parkinson disease (PD)

• Describe the clinical features of idiopathic PD and differentiate between cardinal motor features and non-motor symptoms

• Discuss various risk factors and corresponding mechanisms responsible for the development of PD symptoms

• Review biosynthesis of dopamine, its metabolic outcomes, dopaminergic pathways, receptor distribution and corresponding signal transduction mechanisms

• Explain in detail the pathophysiologic mechanisms responsible for the clinical features of idiopathic PD

• Evaluate the clinical role of L-DOPA and discuss its mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

• For each medication class listed below, discuss their mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

o Dopamine agonists

▪ ropinirole (Requip®, Requip® XL); pramipexole Mirapex®, Mirapex® ER); rotigotine transdermal patch (Neupro®), and apomorphine (Apokyn®)

o Catechol-O-methyltransferase (COMT) inhibitors

▪ entacapone (Comtan®) and tolcapone (Tasmar®)

o Selective monoamine oxidase-B (MAO- B) inhibitors

▪ selegiline (Eldepryl® and Zelapar® ODT) and rasagiline (Azilect®)

▪ amantadine (Symmetrel®)

o Anticholinergic agents (benztropine (Cogentin®) and trihexyphenidyl)


Keywords: Parkinson’s disease (PD), Amantadine, Anticholinergic agents, Antiparkinsonian drugs, Apomorphine, Benztropine, Catechol-- -methyltransferase (COMT) inhibitors, Dopamine (DA), Entacapone, L-DOPA dopamine agonists, Muscarinic agents, Pramipexole, Rasagiline, Ropinirole, Rotigotine, Selective monoamine oxidase-B (MAO-B) inhibitors, Tolcapone, Selegiline, Structure-activity relationshipand drug-receptor.

Related Journals

Related Books

Request history8.2.27PHP Version155msRequest Duration26MBMemory UsageGET chapter/{id}/{param?}Route
  • warninglog[23:10:47] LOG.warning: Optional parameter $id declared before required parameter $request is implic...
  • Booting (89.23ms)time
  • Application (65.79ms)time
  • 1 x Booting (57.56%)
    89.23ms
    1 x Application (42.44%)
    65.79ms
    11 templates were rendered
    • ebook.chapter_detailschapter_details.blade.php#?blade
    • layouts.chapter_header_sectionchapter_header_section.blade.php#?blade
    • ebook.chapter_top_bannerchapter_top_banner.blade.php#?blade
    • ebook.chapter_bottom_bannerchapter_bottom_banner.blade.php#?blade
    • ebook.ebook_right_bannerebook_right_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET chapter/{id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ChapterController@GetChapterDetails
    namespace
    App\Http\Controllers
    where
    as
    chapter
    file
    app/Http/Controllers/ChapterController.php:1349-1703
    19 statements were executed11.87ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('51321204','',1,1737069047,1737069047) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1737069047
      910μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('51321204','/chapter/14009',1,1737069047,1737069047)
      140μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51321204 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51321204) limit 1
      3.74msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51321204
      • 1: 51321204
      • 2: 51321204
      • 3: 51321204
      • 4: 51321204
      • 5: 51321204
      • 6: 51321204
      • 7: 51321204
      • 8: 51321204
      • 9: 51321204
      • 10: 51321204
      • 11: 51321204
      • 12: 51321204
      • 13: 51321204
      • 14: 51321204
      • 15: 51321204
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:63
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • select * from `chapter` where `chapter_id` = '14009' limit 1
      260μsalphaeurekaselec_live_10_06_2022ChapterController.php#1405
      Bindings
      • 0: 14009
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1405
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs , `au`.*, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`chapter_id` = '14009' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      590μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 14009
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ChapterController.php:1410
      • 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 * from `keywords` where `chapter_id` = '14009'
      290μsalphaeurekaselec_live_10_06_2022ChapterController.php#1414
      Bindings
      • 0: 14009
      Backtrace
      • 15. app/Http/Controllers/ChapterController.php:1414
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select * from `ebook` where `ebook_id` = 706 limit 1
      200μsalphaeurekaselec_live_10_06_2022ChapterController.php#1429
      Bindings
      • 0: 706
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1429
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select count(*) as aggregate from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=706) and se.ebook_id!=706 and v.ebook_status='1'
      960μsalphaeurekaselec_live_10_06_2022Subject.php#236
      Backtrace
      • 16. app/Models/Subject.php:236
      • 17. app/Http/Controllers/ChapterController.php:1433
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=706) and se.ebook_id!=706 and v.ebook_status='1' limit 10 offset 0
      630μsalphaeurekaselec_live_10_06_2022Subject.php#236
      Backtrace
      • 14. app/Models/Subject.php:236
      • 15. app/Http/Controllers/ChapterController.php:1433
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as aggregate from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=706)
      350μsalphaeurekaselec_live_10_06_2022Subject.php#253
      Backtrace
      • 16. app/Models/Subject.php:253
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct j.nid as journal_nid,j.title,j.subtitle,j.issn,j.eissn,j.keyword,sj.journal_id,j.image_file_name,j.flyer_link from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=706) limit 10 offset 0
      430μsalphaeurekaselec_live_10_06_2022Subject.php#253
      Backtrace
      • 14. app/Models/Subject.php:253
      • 15. app/Http/Controllers/ChapterController.php:1434
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `e`.*, `a`.*, `y`.`year`, `e`.`ebook_volume_id` as `ebook_volume_id`, `a`.`ebook_volume_id` as `ebk_vol_id`, `e`.`ebook_id` as `ebk_ebook_id` from `ebook_volume` as `e` left join `author` as `a` on `e`.`ebook_volume_id` = `a`.`ebook_volume_id` left join `year` as `y` on `y`.`id` = `e`.`year_id` where `e`.`ebook_volume_id` = 2884 and `e`.`is_uploaded` = 1
      470μsalphaeurekaselec_live_10_06_2022EbookVolume.php#271
      Bindings
      • 0: 2884
      • 1: 1
      Backtrace
      • 13. app/Models/EbookVolume.php:271
      • 14. app/Http/Controllers/ChapterController.php:1437
      • 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 count(*) rcd from `ebook_volume` where `ebook_id` = 706 and ebook_volume_id <> 2884 limit 1
      230μsalphaeurekaselec_live_10_06_2022EbookVolume.php#999
      Bindings
      • 0: 706
      Backtrace
      • 14. app/Models/EbookVolume.php:999
      • 15. app/Http/Controllers/ChapterController.php:1461
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '14009' and content_type = 'c' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      260μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1464
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '2884' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      230μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1477
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2884) 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2884) 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2884)
      520μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1517
      • 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 <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14009) 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 <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14009) 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 <= 51321204 and j.to_ip >=51321204 )) and ((j.from_date <= 1737069047 and j.to_date >= 1737069047 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14009)
      480μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1548
      • 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` = 2884 and `b`.`banner_from_date` <= 1737069047 and `b`.`banner_to_date` >= 1737069047 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.01msalphaeurekaselec_live_10_06_2022Banner.php#189
      Bindings
      • 0: 1
      • 1: B
      • 2: 2884
      • 3: 1737069047
      • 4: 1737069047
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:189
      • 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='ce988d225c04f49186a84397166ccb22'
      170μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._main_menu:13
      • 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
    19Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        o6ld2DIrtlEpgP6tr3oqVscrud5V3zVt0AREw81h
        uc_cart_id
        ce988d225c04f49186a84397166ccb22
        _previous
        array:1 [ "url" => "https://beta.benthamscience.com/chapter/14009" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/14009
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "beta.benthamscience.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "XSRF-TOKEN=eyJpdiI6IklJbk15bWNxQzdxbDhxUVdNUmgxdUE9PSIsInZhbHVlIjoicklTbmNZSXU5UGN5bGR2dEdtemV2cDZBci84cnlrVitxNkJMeW5lSlVPc0JzbUNEWkl4cUdKZHZlQ2pPeGp1MElnUXBDZTErUThZMFpXYmFUaTVGZWt6cDM3ZU9ML0p3YkIzTHFyR2dPOXhoc1hYaDg2NGMrVkx6LzU1cUlnWmIiLCJtYWMiOiI0ZGIwZDM2NjdhMjRhMmFhNjE4ZTE1NTlkZjIxODU3ZDcwNjA3YWExN2Q1NDk3ZDEwMjZmYjJmM2ZjNzU0YTk2IiwidGFnIjoiIn0%3D; eurekaselectnew_session=eyJpdiI6InFwU1hIYkdPSnhDWkpMb1NxeURtTmc9PSIsInZhbHVlIjoiWVMrRDRkSy9RamNyYWFzSTlWTTMwSCtyWGw5bkVXWGpiZUVaN0hITDJqYUEyUnZ6WVd4d0JZWHhqeDQ2d25vcXk5eGJPN1ZFSGlEd3NXRnUxSzNHQ3Y1ZTZ0L1paamFpUXovTlBaYlNobzRDQWxiM0RPREgrR3BMeWxPajk2UWkiLCJtYWMiOiIxODlhYTFjMDYzNDA2YWJlMzc4MGVhZDE5ZDI5MGNhODliY2M2OGQwM2M3YWExMDc1NTRlYjU5YjI4OGRjYWFmIiwidGFnIjoiIn0%3D; _ga_9F3B5VV3T3=GS1.1.1737069046.1.0.1737069046.60.0.0; _ga=GA1.1.69158088.1737069046XSRF-TOKEN=eyJpdiI6IklJbk15bWNxQzdxbDhxUVdNUmgxdUE9PSIsInZhbHVlIjoicklTbmNZSXU5UGN5bGR2dEdtemV2cDZBci84cnlrVitxNkJMeW5lSlVPc0JzbUNEWkl4cUdKZHZlQ2pPeGp1MElnUXBDZ" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "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" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:4 [ "XSRF-TOKEN" => "o6ld2DIrtlEpgP6tr3oqVscrud5V3zVt0AREw81h" "eurekaselectnew_session" => "e2IIFkWf95Pz9wdWKjlvmlEOVQF0ik1mWbi0BkIu" "_ga_9F3B5VV3T3" => null "_ga" => 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 => "Thu, 16 Jan 2025 23:10:47 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkVPcC9ZZkVXVFNYaG9ORWtaS1JyakE9PSIsInZhbHVlIjoiZ2tjN0dSMXB2MGk0UmFub1dRRVFKS29TaVZMM3JUK3hOTktXSGNoRE92SFoweG5hQ0RhVTE0Vm9DK1hXS2ZJVDVvdmJtN3hTSkNRY0J1SkNwYU9Mc3ZEbitybG5uVXRTeHBMODdBVVVLM0VQUFZCM2RBSVNORkY1UjdwRzJZRlMiLCJtYWMiOiJhZDExNDQ3Yzg3YTc2MWIxYjBhYmU2MzAzZjE3MDM0ZGUwODgyMWNiNGNiZjA1ZTBjMzE5ODUzYTA1NDc3MmI1IiwidGFnIjoiIn0%3D; expires=Sun, 19 Jan 2025 11:10:47 GMT; Max-Age=216000; path=/; secure; samesite=strictXSRF-TOKEN=eyJpdiI6IkVPcC9ZZkVXVFNYaG9ORWtaS1JyakE9PSIsInZhbHVlIjoiZ2tjN0dSMXB2MGk0UmFub1dRRVFKS29TaVZMM3JUK3hOTktXSGNoRE92SFoweG5hQ0RhVTE0Vm9DK1hXS2ZJVDVvdmJtN" 1 => "eurekaselectnew_session=eyJpdiI6ImgwVEpIMktybm9uUHg3bldQMFdjbkE9PSIsInZhbHVlIjoibXVaWVVla05zQWM1enJkbVJSWVJ3MWhYK0lrQUh6UHh3Y1g5VGwydkFiYlNFbmVNQ2tSejFMWHQwcjdOWUcxZkdMbzgxUEVzNklMTWRucy9LUWlOMVZaY3BNWDVKaTNrdkpLL3BRNTFadWtJMHh3dzVyc0dyL3J2c29BRktLYTAiLCJtYWMiOiJhODEwMmIzMzc2YjAyOWQxNTAzZDU3NjgyZjdmYjgzNzI3MTUwOTM0NmNhY2FjYmYzM2ZkMDc1MzQzMWVkZGY5IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=stricteurekaselectnew_session=eyJpdiI6ImgwVEpIMktybm9uUHg3bldQMFdjbkE9PSIsInZhbHVlIjoibXVaWVVla05zQWM1enJkbVJSWVJ3MWhYK0lrQUh6UHh3Y1g5VGwydkFiYlNFbmVNQ2tSejFMWHQwcjdO" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkVPcC9ZZkVXVFNYaG9ORWtaS1JyakE9PSIsInZhbHVlIjoiZ2tjN0dSMXB2MGk0UmFub1dRRVFKS29TaVZMM3JUK3hOTktXSGNoRE92SFoweG5hQ0RhVTE0Vm9DK1hXS2ZJVDVvdmJtN3hTSkNRY0J1SkNwYU9Mc3ZEbitybG5uVXRTeHBMODdBVVVLM0VQUFZCM2RBSVNORkY1UjdwRzJZRlMiLCJtYWMiOiJhZDExNDQ3Yzg3YTc2MWIxYjBhYmU2MzAzZjE3MDM0ZGUwODgyMWNiNGNiZjA1ZTBjMzE5ODUzYTA1NDc3MmI1IiwidGFnIjoiIn0%3D; expires=Sun, 19-Jan-2025 11:10:47 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkVPcC9ZZkVXVFNYaG9ORWtaS1JyakE9PSIsInZhbHVlIjoiZ2tjN0dSMXB2MGk0UmFub1dRRVFKS29TaVZMM3JUK3hOTktXSGNoRE92SFoweG5hQ0RhVTE0Vm9DK1hXS2ZJVDVvdmJtN" 1 => "eurekaselectnew_session=eyJpdiI6ImgwVEpIMktybm9uUHg3bldQMFdjbkE9PSIsInZhbHVlIjoibXVaWVVla05zQWM1enJkbVJSWVJ3MWhYK0lrQUh6UHh3Y1g5VGwydkFiYlNFbmVNQ2tSejFMWHQwcjdOWUcxZkdMbzgxUEVzNklMTWRucy9LUWlOMVZaY3BNWDVKaTNrdkpLL3BRNTFadWtJMHh3dzVyc0dyL3J2c29BRktLYTAiLCJtYWMiOiJhODEwMmIzMzc2YjAyOWQxNTAzZDU3NjgyZjdmYjgzNzI3MTUwOTM0NmNhY2FjYmYzM2ZkMDc1MzQzMWVkZGY5IiwidGFnIjoiIn0%3D; path=/; secure; httponlyeurekaselectnew_session=eyJpdiI6ImgwVEpIMktybm9uUHg3bldQMFdjbkE9PSIsInZhbHVlIjoibXVaWVVla05zQWM1enJkbVJSWVJ3MWhYK0lrQUh6UHh3Y1g5VGwydkFiYlNFbmVNQ2tSejFMWHQwcjdO" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "o6ld2DIrtlEpgP6tr3oqVscrud5V3zVt0AREw81h" "uc_cart_id" => "ce988d225c04f49186a84397166ccb22" "_previous" => array:1 [ "url" => "https://beta.benthamscience.com/chapter/14009" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-01-16 23:10:47GET/chapter/140091111921