Abstract
In our pursuit to identify selective ligands for Bz/GABA(A) receptor subtypes, a novel pyrazolo[1,5-a]pyrimidine derivative (4), the azaisostere of zolpidem, was synthesized and evaluated in vitro on bovine brain homogenate and on recombinant benzodiazepine receptors (alphaxbeta2/3gamma2, x = 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha1beta2gamma2 subtype (K(i) = 31 nM), and in an in-depth, in vivo study it revealed sedative and anxiolytic-like properties without any amnesic and myorelaxant effects in rodents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Anxiety Agents / chemical synthesis*
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Anti-Anxiety Agents / chemistry
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Anti-Anxiety Agents / pharmacology
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Anticonvulsants / chemical synthesis
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Anticonvulsants / chemistry
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Anticonvulsants / pharmacology
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Avoidance Learning / drug effects
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Binding, Competitive
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Brain / metabolism
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Cattle
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Cell Line
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GABA-A Receptor Agonists*
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Humans
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Hypnotics and Sedatives / chemical synthesis*
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Hypnotics and Sedatives / chemistry
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Hypnotics and Sedatives / pharmacology
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In Vitro Techniques
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Mice
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Muscle Relaxation / drug effects
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / physiology
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Radioligand Assay
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Rats
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Receptors, GABA-A
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Recombinant Proteins / metabolism
Substances
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Anti-Anxiety Agents
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Anticonvulsants
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GABA-A Receptor Agonists
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GABRA1 protein, human
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Gabra1 protein, mouse
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Hypnotics and Sedatives
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N,N-dimethyl-(2-(4-methylphenyl)-5-methylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
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Pyrazoles
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Pyrimidines
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Receptors, GABA-A
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Recombinant Proteins