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An Overview of the Preclinical Aspects of Topiramate: Pharmacology, Pharmacokinetics, and Mechanism of Action
Abstract
Summary: In this overview, we discuss the discovery and development of topiramate (TPM) as an anticonvulsant, including notable aspects of its chemical, biologic, and pharmacokinetic properties. In particular, we highlight its anticonvulsant profile in traditional seizure tests and animal models of epilepsy and the results of recent electrophysiological and biochemical studies using cultured neurons that have revealed a unique combination of pharmacologic properties of TPM. Finally, we present a hypothesis for the mechanistic basis of the anticonvulsant activity of TPM, which proposes that TPM binds to certain membrane ion channel proteins at phosphory‐lation sites and thereby allosterically modulates channel conductance and secondarily inhibits protein phosphorylation.
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Cited by
Diener, H.-C., Bussone, G., Oene, J. V., Lahaye, M., Schwalen, S., & Goadsby, P. (2007) · Cephalalgia · doi:10.1111/j.1468-2982.2007.01326.x · Cited by 561
Medication treatment of different types of alcoholism
Johnson, B. A. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.08101500 · Cited by 151
Biochemical and stone-risk profiles with topiramate treatment
Welch, B. J., Graybeal, D., Moe, O. W., Maalouf, N. M., & Sakhaee, K. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.07.003 · Cited by 126
Existing and future drugs for the treatment of the dark side of addiction
Koob, G. F., & Mason, B. J. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103143 · Cited by 121
Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review
Fischler, P. V., Soyka, M., Seifritz, E., & Mutschler, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.927703 · Cited by 34
Metadata
- Authors
- Shank, R. P., Gardocki, J. F., Streeter, A. J., & Maryanoff, B. E.
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2000-01
- Volume
- 41
- Issue
- s1
- Pages
- 3-9
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W2083322751
- Cited by
- 810
- References
- 0
- FWCI
- 18.05
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Shank, R. P., Gardocki, J. F., Streeter, A. J., & Maryanoff, B. E. (2000). An Overview of the Preclinical Aspects of Topiramate: Pharmacology, Pharmacokinetics, and Mechanism of Action. Epilepsia. https://doi.org/10.1111/j.1528-1157.2000.tb02163.x
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