Abstract
In the recent study we have extended our investigations to the new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid (GHB). Among the obtained compounds N-benzylamide of alpha-(1,2,3,4-tetrahydroisoquinoline)-GHB (9) has demonstrated activity against maximal electroshock (MES) induced seizures in mice (at 100 mg/kg ip) and in rats (at 30 mg/kg, po dose). Lactone 8 and amide 9 have possessed a weak effect on [3H]-muscimol binding. Molecular modeling studies have revealed that anticonvulsant activity of the alpha-substituted amides of GHB might partially be explained by the orientation of the terminal benzylamide fragment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticonvulsants / chemical synthesis
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Anticonvulsants / chemistry
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Anticonvulsants / pharmacology
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Benzyl Compounds / chemical synthesis*
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Benzyl Compounds / chemistry
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Benzyl Compounds / pharmacology*
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Drug Design
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Drug Evaluation, Preclinical / methods
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Electroshock
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GABA Agents / chemical synthesis
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GABA Agents / chemistry
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GABA Agents / pharmacology*
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Hydroxybutyrates / chemistry*
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Injections, Intraperitoneal
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Injections, Subcutaneous
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Male
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Mice
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Models, Chemical
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Molecular Structure
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Pentylenetetrazole / administration & dosage
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Pentylenetetrazole / toxicity
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Seizures / chemically induced
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Seizures / drug therapy
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Seizures / prevention & control
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Tritium
Substances
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Anticonvulsants
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Benzyl Compounds
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GABA Agents
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Hydroxybutyrates
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Tritium
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4-hydroxybutyric acid
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Pentylenetetrazole