Anticonvulsant Activity of Glycylglycine and δ‐Aminovaleric Acid: Evidence for Glutamine Exchange in Amino Acid Transport
Abstract
We have proposed that glutamine serves in a facilitated diffusion process, mediated by the enzyme gamma-glutamyl transferase (gamma-glutamyl transpeptidase; gamma GT) and that it leaves the brain in exchange for entering amino acids. Glutamine is also a precursor of gamma-aminobutyric acid (GABA). Thus, providing an alternate substrate for gamma GT should spare brain glutamine, raise GABA, and cause an anticonvulsant effect. We have found that glycylglycine, the best-known substrate for gamma GT, and delta-aminovaleric acid (DAVA), a structural analog, have anticonvulsant activity in DBA/2J mice. Both compounds can decrease the incidence and severity of seizures induced by L-methionine-RS-sulfoximine or electroconvulsive shock. DAVA was also tested and found to be active against seizures caused by pentylenetetrazol or picrotoxin. [14C]DAVA entered the brain at the rate of 18.7 nmol/g/min. The activity of DAVA as a substrate of gamma GT was intermediate to that of glycylglycine and glutamine. Preliminary studies have shown that brain glutamine and perhaps GABA are elevated 3 h after administration of DAVA (7.5 mmol/kg). These findings support the theory that glutamine exchange plays a role in amino acid transport across the blood-brain barrier and suggests a new concept in anticonvulsant therapy.
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5AV acts as an anticonvulsant in mice.
“5AV acts as an anticonvulsant in mice (Dhaher et al., 2014; Samuels et al., 1983).”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as Samuels et al., 1983
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Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
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- Authors
- Samuels, S., Fish, I., & Schwartz, S. A.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Samuels, Stanley
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1983-04
- Volume
- 40
- Issue
- 4
- Pages
- 1063-1068
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2045650983
- Cited by
- 14
- References
- 25
- Citations by year
- 2025: 1 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- glycylglycine, delta-aminovaleric acid, anticonvulsant activity, amino acid transport, blood-brain barrier, gamma-glutamyl transferase, GABA, seizures, electroconvulsive shock, pentylenetetrazole, picrotoxin, DBA/2J mice, brain glutamine
- MeSH terms
- Amino Acids, Animals, Anticonvulsants, Biological Transport, Brain, Dipeptides, Electroshock, Female, Glutamine, Glycylglycine, Intestine, Small, Kidney, Liver, Mice, Inbred DBA, Muscles, Seizures, Amino Acids, Neutral, Mice
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