Katsuya Suemaru1, Misato Yoshikawa2, Hiroaki Aso3, Masahiko Watanabe4. 1. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan. Electronic address: ksuemaru@shujitsu.ac.jp. 2. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan. Electronic address: yoshikawa@shujitsu.ac.jp. 3. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan. Electronic address: aso@shujitsu.ac.jp. 4. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan. Electronic address: wa1@shujitsu.ac.jp.
Abstract
OBJECTIVE: Acetaminophen is one of the most commonly used analgesic and antipyretic drugs. It has been reported that acetaminophen has anticonvulsant effects in several animal models of seizure. An active metabolite of acetaminophen, AM404, inhibits the uptake of the endocannabinoid anandamide. However, the mechanism of the anticonvulsant effect of acetaminophen is unknown. METHODS: This study was performed to examine whether or not acetaminophen can protect against pentylenetetrazol-induced kindling in mice and to investigate the precise mechanisms of the anticonvulsant effect of acetaminophen using the fully kindled mouse models. RESULTS: Repeated administration of acetaminophen significantly delayed the progression of seizure severity induced by pentylenetetrazol. Additionally, acetaminophen showed a dose-dependent anticonvulsant activity against fully pentylenetetrazol-kindled seizures. AM404 also exhibited a dose-dependent anticonvulsant activity in fully kindled animals. The anticonvulsant activity of acetaminophen was antagonized by capsazepine and AMG9810, two transient receptor potential vanilloid-1 (TRPV1) antagonists. However, the transient receptor potential ankyrin 1 (TRPA1) antagonist HC030031 and CB1 receptor antagonist AM251 had no effect. CONCLUSION: These findings suggest that acetaminophen has an anticonvulsant effect in pentylenetetrazol-kindled mouse models and TRPV1 mediates the anticonvulsant action.
OBJECTIVE:Acetaminophen is one of the most commonly used analgesic and antipyretic drugs. It has been reported that acetaminophen has anticonvulsant effects in several animal models of seizure. An active metabolite of acetaminophen, AM404, inhibits the uptake of the endocannabinoidanandamide. However, the mechanism of the anticonvulsant effect of acetaminophen is unknown. METHODS: This study was performed to examine whether or not acetaminophen can protect against pentylenetetrazol-induced kindling in mice and to investigate the precise mechanisms of the anticonvulsant effect of acetaminophen using the fully kindled mouse models. RESULTS: Repeated administration of acetaminophen significantly delayed the progression of seizure severity induced by pentylenetetrazol. Additionally, acetaminophen showed a dose-dependent anticonvulsant activity against fully pentylenetetrazol-kindled seizures. AM404 also exhibited a dose-dependent anticonvulsant activity in fully kindled animals. The anticonvulsant activity of acetaminophen was antagonized by capsazepine and AMG9810, two transient receptor potential vanilloid-1 (TRPV1) antagonists. However, the transient receptor potential ankyrin 1 (TRPA1) antagonist HC030031 and CB1 receptor antagonist AM251 had no effect. CONCLUSION: These findings suggest that acetaminophen has an anticonvulsant effect in pentylenetetrazol-kindled mouse models and TRPV1 mediates the anticonvulsant action.
Authors: Omar M E Abdel-Salam; Amany A Sleem; Marawan Abd El Baset Mohamed Sayed; Eman R Youness; Nermeen Shaffie Journal: Neurochem Res Date: 2020-02-08 Impact factor: 3.996
Authors: Karen Jaqueline Paredes-Ruiz; Karla Chavira-Ramos; Mario Orozco-Morales; Cimen Karasu; Alexey A Tinkov; Michael Aschner; Abel Santamaría; Ana Laura Colín-González Journal: Neurotox Res Date: 2021-11-06 Impact factor: 3.911
Authors: Katarzyna Magierowska; Dominik Bakalarz; Dagmara Wójcik; Edyta Korbut; Aleksandra Danielak; Urszula Głowacka; Robert Pajdo; Grzegorz Buszewicz; Grzegorz Ginter; Marcin Surmiak; Sławomir Kwiecień; Anna Chmura; Marcin Magierowski; Tomasz Brzozowski Journal: Cells Date: 2020-05-12 Impact factor: 6.600
Authors: Adam Stasiulewicz; Katarzyna Znajdek; Monika Grudzień; Tomasz Pawiński; And Joanna I Sulkowska Journal: Int J Mol Sci Date: 2020-04-16 Impact factor: 5.923
Authors: Katarzyna Magierowska; Dagmara Wojcik; Anna Chmura; Dominik Bakalarz; Mateusz Wierdak; Slawomir Kwiecien; Zbigniew Sliwowski; Tomasz Brzozowski; Marcin Magierowski Journal: Int J Mol Sci Date: 2018-09-28 Impact factor: 5.923