Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Epilepsy*/metabolism ; Trimetazidine*/pharmacology ; Trimetazidine*/therapeutic use; Animals ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Avoidance Learning ; Brain/metabolism ; Carbamazepine/pharmacology ; Carbamazepine/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Interactions ; Drug Synergism ; Electroshock/adverse effects ; Mice ; Phenobarbital/pharmacology ; Phenobarbital/therapeutic use ; Phenytoin ; Valproic Acid/therapeutic use

Trimetazidine (TMZ), an anti-ischemic drug for improving cellular metabolism, is mostly administered to patients with poorly controlled ischemic heart disease (IHD). Since IHD is considered the most frequent causative factor of cardiac arrhythmias, and these often coexist with seizure disorders, we decided to investigate the effect of TMZ in the electroconvulsive threshold test (ECT) and its influence on the action of four first-generation antiepileptic drugs in the maximal electroshock test (MES) in mice. The TMZ (up to 120 mg/kg) did not affect the ECT, but applied at doses of 20-120 mg/kg it decreased the antielectroshock action of phenobarbital. The TMZ (50-120 mg/kg) reduced the effect of phenytoin, and, when administered at a dose of 120 mg/kg, it diminished the action of carbamazepine. All of these revealed interactions seem to be pharmacodynamic, since the TMZ did not affect the brain levels of antiepileptic drugs. Furthermore, the combination of TMZ with valproate (but not with other antiepileptic drugs) significantly impaired motor coordination, evaluated using the chimney test. Long-term memory, assessed with a passive-avoidance task, was not affected by either the TMZ or its combinations with antiepileptic drugs. The obtained results suggest that TMZ may not be beneficial as an add-on therapy in patients with IHD and epilepsy.

Brain Behav Immun. 2021 Nov;98:110-121. (PMID: 34403737)
Naunyn Schmiedebergs Arch Pharmacol. 2011 Apr;383(4):385-92. (PMID: 21318336)
Neuropharmacology. 2005 Sep;49(4):456-64. (PMID: 15913671)
Can J Physiol Pharmacol. 2017 Jun;95(6):686-696. (PMID: 28177664)
Am J Ther. 2016 May-Jun;23(3):e871-9. (PMID: 25756467)
Brain Res. 2009 Dec 8;1301:52-60. (PMID: 19765566)
Mol Cell Neurosci. 2004 Apr;25(4):732-41. (PMID: 15080900)
Neuropharmacology. 2011 Dec;61(8):1256-64. (PMID: 21839100)
Metabolism. 2016 Mar;65(3):122-30. (PMID: 26892523)
PLoS One. 2012;7(9):e45618. (PMID: 23029138)
Eur J Pharmacol. 1986 Aug 22;128(1-2):55-65. (PMID: 3758188)
Clin Exp Pharmacol Physiol. 2008 May;35(5-6):630-7. (PMID: 18318745)
Basic Clin Pharmacol Toxicol. 2010 May;106(5):372-7. (PMID: 20002063)
Acta Med Iran. 2015;53(1):17-24. (PMID: 25597600)
Int J Mol Sci. 2021 Mar 03;22(5):. (PMID: 33802323)
Eur J Pharmacol. 2007 Nov 21;574(1):8-14. (PMID: 17658512)
Seizure. 2010 Jun;19(5):300-2. (PMID: 20444628)
Eur J Pharmacol. 2021 Jul 15;903:174150. (PMID: 33961874)
J Pharmacol Exp Ther. 1949 Jun;96(2):99-113. (PMID: 18152921)
Mol Psychiatry. 2017 Apr;22(4):595-604. (PMID: 27431292)
Neurochem Res. 2008 Jul;33(7):1373-83. (PMID: 18302021)
Synapse. 1996 Feb;22(2):159-94. (PMID: 8787131)
Free Radic Biol Med. 2004 Dec 15;37(12):1951-62. (PMID: 15544915)
FASEB J. 2008 Mar;22(3):659-61. (PMID: 17942826)
Eur J Pharmacol. 1991 Mar 19;195(1):157-62. (PMID: 1829682)
Neuroscience. 1993 Mar;53(2):425-31. (PMID: 8098511)
Pharmacol Rep. 2020 Oct;72(5):1218-1226. (PMID: 32865811)
Pharmacol Rep. 2006 Jul-Aug;58(4):559-61. (PMID: 16963803)
Semin Neurol. 2020 Dec;40(6):617-623. (PMID: 33155183)
Nature. 1986 Jun 26-Jul 2;321(6073):864-6. (PMID: 3724846)
J Pharmacol Exp Ther. 2003 Aug;306(2):523-7. (PMID: 12730361)
Chin Med Sci J. 2004 Dec;19(4):242. (PMID: 15669178)
Pharmacology. 2005 Nov;75(3):122-32. (PMID: 16155371)
Methods Find Exp Clin Pharmacol. 2009 Mar;31(2):101-6. (PMID: 19455265)
Biomed Res Int. 2019 Nov 14;2019:1767203. (PMID: 31815123)
Eur Neurol. 2007;57(2):65-9. (PMID: 17179706)
Int J Mol Sci. 2022 Mar 07;23(5):. (PMID: 35270033)
Neuropharmacology. 2020 May 15;168:107966. (PMID: 32120063)
Pharmacol Toxicol. 1993 Apr-May;72(4-5):213-20. (PMID: 8103921)
Neuropsychiatr Dis Treat. 2018 Mar 16;14:787-797. (PMID: 29588593)
Epilepsy Res. 2018 Feb;140:105-110. (PMID: 29329017)
ScientificWorldJournal. 2013 Oct 22;2013:686304. (PMID: 24250273)

473 Medical University of Lublin

Keywords: drug interactions; first-generation antiepileptic drugs; maximal electroshock; trimetazidine

0 (Anticonvulsants)
33CM23913M (Carbamazepine)
614OI1Z5WI (Valproic Acid)
6158TKW0C5 (Phenytoin)
N9A0A0R9S8 (Trimetazidine)
YQE403BP4D (Phenobarbital)

Date Created: 20221014 Date Completed: 20221017 Latest Revision: 20221019

20250114

PMC9570019

10.3390/ijms231911328

36232629