Abstract |
Glycine is a small neutral amino acid exhibiting weak anticonvulsant activities in vivo. Recently, studies have demonstrated that N-(benzyloxycarbonyl) glycine (1) antagonized seizures superior to glycine in addition to activity in the maximal electroshock (MES) test, a convulsive model where glycine is inactive. In the present study a series of ester and amide derivatives of 1 as well as esters of N-(3-phenylpropanoyl)glycine (5) have been prepared. The compounds were evaluated in the MES test as well as in several chemically induced seizure models. Among the derivatives investigated, N-(benzyloxycarbonyl) glycine benzylamide (16) was the most potent compound exhibiting an anticonvulsant activity in the MES test comparable to the drug phenytoin. Median effective doses (ED50) of 4.8 and 11.6 mg/kg were determined at 30 min and 3 h after i.p. administration, respectively. Compound 16 also effectively suppressed tonic seizures in different chemically induced models such as the strychnine, 3-mercaptopropionic acid, and pentylenetetrazole tests. Moreover, the compound studied here did not show acute neurotoxicity in the rotorod test up to a dose of 150 mg/kg. It is concluded that N-(benzyloxycarbonyl) glycine amides, especially 16, are potent anticonvulsant agents.
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Authors | M Geurts, J H Poupaert, G K Scriba, D M Lambert |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 41
Issue 1
Pg. 24-30
(Jan 01 1998)
ISSN: 0022-2623 [Print] United States |
PMID | 9438018
(Publication Type: Journal Article)
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Chemical References |
- Amides
- Anticonvulsants
- Esters
- Neurotoxins
- Receptors, Glycine
- 3-Mercaptopropionic Acid
- Strychnine
- Glycine
- Pentylenetetrazole
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Topics |
- 3-Mercaptopropionic Acid
- Amides
- Animals
- Anticonvulsants
(chemical synthesis, chemistry, pharmacology)
- Dose-Response Relationship, Drug
- Electroshock
- Esters
- Glycine
(analogs & derivatives, metabolism, pharmacology)
- Male
- Mice
- Mice, Inbred Strains
- Neurotoxins
(pharmacology)
- Pentylenetetrazole
- Radioligand Assay
- Rats
- Rats, Wistar
- Receptors, Glycine
(drug effects, metabolism)
- Seizures
(chemically induced, etiology, prevention & control)
- Spinal Cord
(metabolism)
- Strychnine
(pharmacology)
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