Abstract
Two new GABA derivatives, 1 and 2, were synthesized and tested for their capacity to display CNS activity, which was assessed by determining the effects on the duration of pentobarbital-induced hypnosis in rats. Compound 1, peripherally injected, significantly prolonged the hypnosis time, a typical GABA-mimetic effect, while both intracerebroventricular and intravenous administration of compound 2 surprisingly shortened the hypnotic effect in an atropine-sensitive way. The study was extended also to compounds 1a, 1b and 2a, putative oxidative/hydrolytic metabolites of 1 and 2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Atropine / pharmacology
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Binding, Competitive
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Biotransformation
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Blood-Brain Barrier / drug effects*
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Dose-Response Relationship, Drug
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Female
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Hydrolysis
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Hypnotics and Sedatives / pharmacology
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Injections, Intraperitoneal
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Injections, Intravenous
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Injections, Intraventricular
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Magnetic Resonance Spectroscopy
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Muscarinic Antagonists / pharmacology
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Oxidation-Reduction
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Pentobarbital / pharmacology
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Rats
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Rats, Wistar
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Receptors, GABA-A / drug effects
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Receptors, GABA-A / metabolism
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Receptors, GABA-B / drug effects
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Receptors, GABA-B / metabolism
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Sleep / drug effects
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gamma-Aminobutyric Acid / analogs & derivatives*
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gamma-Aminobutyric Acid / metabolism
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gamma-Aminobutyric Acid / pharmacokinetics*
Substances
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Hypnotics and Sedatives
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Muscarinic Antagonists
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Receptors, GABA-A
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Receptors, GABA-B
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gamma-Aminobutyric Acid
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Atropine
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Pentobarbital