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Seizure Protection and Increased Nerve-Terminal GABA: Delayed Effects of GABA Transaminase Inhibition
Abstract
Changes in γ-aminobutyric acid (GABA) occurring in the presence and in the absence of GABA-containing nerve terminals were estimated in rats in which the dense GABA projection to the substantia nigra was surgically destroyed on one side of the brain. The net increase in GABA of the denervated nigra was compared with that of the intact nigra at various times after a single injection of γ-vinyl-GABA, which irreversibly inhibits GABA transaminase. Total GABA reached a maximum within 12 hours, but the GABA pool associated with nerve terminals did not increase until 36 hours and peaked at 60 hours. The onset and peak of anticonvulsant activity against maximal electroshock seizures directly paralleled the time course for the increase in GABA in nerve terminals, but was not positively correlated with that independent of the terminals. This result supports the concept that elevating GABA in nerve terminals facilitates GABA-mediated synaptic transmission and predicts anticonvulsant activity.
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Citations
Cited by
Substantia Nigra: Site of Anticonvulsant Activity Mediated by γ-Aminobutyric Acid
Iadarola, M. J., & Gale, K. (1982) · Science · doi:10.1126/science.7146907 · Cited by 592
Self-citationMechanism of anticonvulsant action of valproate
Chapman, A., Keane, P. E., Meldrum, B. S., Simiand, J., & Vernieres, J. C. (1982) · Progress in Neurobiology · doi:10.1016/0301-0082(82)90010-7 · Cited by 337
Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies
Gernert, M., & Feja, M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121134 · Cited by 68
Samuels, S., Fish, I., & Schwartz, S. A. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb08093.x · Cited by 14
Metadata
- Authors
- Gale, K., & Iadarola, M. J.
- Venue
- Science
- Published
- 1980-04-18
- Volume
- 208
- Issue
- 4441
- Pages
- 288-291
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1977221546
- Cited by
- 175
- References
- 0
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- closed
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- Gale, K., & Iadarola, M. J. (1980). Seizure Protection and Increased Nerve-Terminal GABA: Delayed Effects of GABA Transaminase Inhibition. Science. https://doi.org/10.1126/science.6768130
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
