Influence of β- blockers on the activity of some anti-epileptic drugs on convulsions induced by picrotoxin in mice
DOI:
https://doi.org/10.54361/ljmr.16210Keywords:
β-blockers, picrotoxin, convulsion, phenytoin, phenobarbitalAbstract
Adrenergic β-receptor blockers are widely used in clinic for the management of cardiovascular disease and some other illnesses. However, this group of drugs known to cause central nervous system side effects such as drowsiness, sleep disturbance, hallucination, migraine and tremors. As anti-epileptic drugs exert their action mainly through the inhibition of the central nervous system to decrease the firing and the excitability of neurons. Accordingly, β-blockers might influence the pharmacological activity of anti-epileptic drugs. Aim:The aims of this study is to investigate the influence of β –blockerson the anti-convulsant activity of two anti-epileptic drugs, i.e. phenytoin and phenobarbital. Methods: Three beta blockers with different β-receptor blocking selectivity and degree of solubility (atenolol, metoprolol, and propranolol) were injected intraperitoneally (IP) into mice either alone or in combination with phenytoin or phenobarbital. After 30 min mice were injected with picrotoxin (8mg/kg) to induce convulsions. Convulsion parameters recorded were; the onset of jerks, number of tonic and clonic convulsions, and % mortality. Results: Picrotoxin produced 100% death in all control animals. However, mosttheanimals treated with antiepileptics alone or in combination with β-blockers were protected from death. The effect of phenytoin on the onset of convulsions was significantlyenhanced when it combined with β-blockers. However, in regard to phenobarbital only the increase was noticed with propranolol. Giving phenytoin with β-blockers improves its effect in reducing clonic convulsion, whereas, no change in phenobarbital activity when administered together with β-blockers. Combination of either phenytoin or phenobarbital with β-blockers did not result in any significant change in their ability to reduce tonic convulsions except when phenytoin co-administered with metoprolol a significant decrease was observed. Conclusion: The administration of β-blockers in concomitant with phenytoin and phenobarbital increased their anticonvulsant activity. However, β-blockers alone could have some protective effect against convulsions.
References
Ahmed, Abdulrzag F et al. 2018. “Roles of β-Adrenergic Receptors on the Mechanism of Action of Imipramine in Chronic Mild Stress Model of Depression.” Lebda Medical Journal 5(1): 168–79. https://elmergib.edu.ly/euj/index.p hp/LMJ/article/view/88 (December 2, 2022).
Ahmed, Abdulrzag F, Rida A Al-Tubuly, Suhera M Aburawi, and Shaban E A Saad. 2017. “The Role of Beta-Adrenergic Receptors in the Mechanism of Action of Imipramine in Forced Swim Test.” Lebda Medical Journal 3(1): 106–13. https://www.elmergib.edu.ly/euj/index.php/LMJ/article/view/80 (December 2, 2022).
Aminoff, Michael J., François Boller, and Dick Swaab. 2022. “Foreword.” Handbook of Clinical Neurology 190: ix–x. DOI: https://doi.org/10.1016/B978-0-12-823384-9.09998-9
Chahine, Mohamed. 2011. “New Insights into Cardiac and Brain Sodium Channels Modulation by Beta Blockers.” Frontiers in Pharmacology 2: 144. /pmc/articles/PMC3134864/ (November 10, 2022). DOI: https://doi.org/10.3389/fphar.2011.00001
Cojocariu, Sabina Alexandra et al. 2021. “Neuropsychiatric.Consequences of Lipophilic Beta-Blockers.” Medicina 2021, Vol. 57, Page 155 57(2): 155. https://www.mdpi.com/1648-9144/57/2/155/htm (November 9, 2022). DOI: https://doi.org/10.3390/medicina57020155
Farzam, Khashayar, and Arif Jan. 2022a. “Beta Blockers.” Drugs in Sport, Seventh Edition: 307–15. https://www.ncbi.nlm.nih.gov/book s/NBK532906/ (November 9, 2022).
———. 2022b. “Beta Blockers.” https://www.ncbi.nlm.nih.gov/book s/NBK532906/ (November 9, 2022).
Ghosh, Shampa et al. 2021. “Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy.” Biomedicines 9(5). /pmc/articles/PMC8146518/ (November 10, 2022). DOI: https://doi.org/10.3390/biomedicines9050470
Goldner, Jonathan A. 2012. “Metoprolol-Induced Visual Hallucinations: A Case Series.” Journal of Medical Case Reports 6(1): 1–3. https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-6-65 (November 5, 2022). DOI: https://doi.org/10.1186/1752-1947-6-65
Kostis, John B, and Raymond C Rosen. 1987. “B-BLOCKADE Central Nervous System Effects of /3-Adrenergic-Blocking Drugs: The Role of Ancillary Properties.” Circulation 75(1): 204–12. http://ahajournals.org (November 10, 2022). DOI: https://doi.org/10.1161/01.CIR.75.1.204
Laurens, Claire, Anne Abot, Alain Delarue, and Claude Knauf. 2019. “Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier.” Frontiers in Neuroscience 13(JAN): 33. DOI: https://doi.org/10.3389/fnins.2019.00033
Laviolette, Steven R et al. 2022. “Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder.” International Journal of Molecular Sciences 2022, Vol. 23, Page 10099 23(17): 10099. https://www.mdpi.com/1422-0067/23/17/10099/htm (November 9, 2022). DOI: https://doi.org/10.3390/ijms231710099
Liu, Yiyun et al. 2015. “Is Pindolol Augmentation Effective in Depressed Patients Resistant to Selective Serotonin Reuptake Inhibitors? A Systematic Review and Meta-Analysis.” Human psychopharmacology 30(3): 132– 42. https://pubmed.ncbi.nlm.nih.gov/2 5689398/ (November 9, 2022). DOI: https://doi.org/10.1002/hup.2465
Magder, Sheldon, Magdi Sami, Ruth Ripley, and Robert Lisbona. 1987. “Comparison of the Effects of Pindolol and Propranolol on Exercise Performance in Patients with Angina Pectoris.” American Journal of Cardiology 59(15): 1289– 94. http://www.ajconline.org/article/0 002914987909064/fulltext (November 9, 2022). DOI: https://doi.org/10.1016/0002-9149(87)90906-4
Maideen, Naina Mohamed Pakkir et al. 2021. “A Review on Pharmacokinetic and Pharmacodynamic Drug Interactions of Adrenergic β-Blockers with Clinically Relevant Drugs-An Overview.” Current drug metabolism 22(9): 672–82. https://pubmed.ncbi.nlm.nih.gov/3 4182907/ (November 9, 2022). DOI: https://doi.org/10.2174/1389200222666210614112529
Martínez-Milla, Juan, Sergio Raposeiras-Roubín, Domingo A. Pascual-Figal, and Borja Ibáñez. 2019. “Role of Beta-Blockers in Cardiovascular Disease in 2019.” Revista Española de Cardiología (English Edition) 72(10): 844–52. http://www.revespcardiol.org/en-role-beta-blockers-in-cardiovascular-disease-articulo-S1885585719301860 (November 9, 2022). DOI: https://doi.org/10.1016/j.rec.2019.04.014
Okuda, Naoki et al. 1999. “EFFECT OF PROPRANOLOL ON CENTRAL NEUROTRANSMITTER RELEASE IN WISTAR RATS ANALYSED BY BRAIN MICRODIALYSIS.” Clinical and Experimental Pharmacology and Physiology 26(3): 220–24. https://onlinelibrary.wiley.com/ (November 9, 2022). DOI: https://doi.org/10.1046/j.1440-1681.1999.03018.x
Sellers, and Lewis. 2022. “Top 50 Prescription Drugs and What They Treat.” https://www.healthgrades.com/right-care/patient-advocate/the-top-50-drugs-prescribed-in-the-united-states (November 9, 2022).
Shah, Rony et al. 2020. “Metoprolol-Associated Central Nervous System Complications.” Cureus 12(5). https://www.cureus.com/articles/3 2391-metoprolol-associated-central-nervous-system-complications (November 9, 2022). DOI: https://doi.org/10.7759/cureus.8236
Tzingounis, Anastassios V., Mark Von Zastrow, and Guillermo A. Yudowski. 2010. “β-Blocker Drugs Mediate Calcium Signaling in Native Central Nervous System Neurons by β-Arrestin-Biased Agonism.” Proceedings of the National Academy of Sciences of the United States of America 107(49): 21028– 33. /pmc/articles/PMC3000286/ (November 10, 2022). DOI: https://doi.org/10.1073/pnas.1004169107
Zaccara, Gaetano, and Simona Lattanzi. 2019. “Comorbidity between Epilepsy and Cardiac Arrhythmias: Implication for Treatment.” Epilepsy & behavior : E&B 97: 304–12. https://pubmed.ncbi.nlm.nih.gov/3 1279643/ (November 11, 2022). DOI: https://doi.org/10.1016/j.yebeh.2019.05.038
Zolkowska, Dorota et al. 2012. “Characterization of Seizures Induced by Acute and Repeated Exposure to Tetramethylenedisulfotetramine.” J DOI: https://doi.org/10.1124/jpet.111.190579
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Shaban E. A. Saad, Suhera M. Aburawi, Ahlaam A Rahoumh, Ahlaam A Rahoumh, Akram Abdraheem (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
