Interaction of 21 benzodiazepine derivatives with the glycine receptor in the brainstem and spinal cord of rat has been evaluated in terms of their displacement of [3H] strychnine binding. The rank order of potency of the 21 drugs in displacing specific [3H] strychnine binding correlates (p < 0.005) with their rank order of potency derivatives in a variety of pharmacologic and behavioral tests in humans and animals that predict clinical efficacy. There is a 50 fold variation in potency of the series of benzodiazepine derivatives with mean effective dose (ED50) values ranging from 19 μM to > 1000 μM. Diazepam and chlordiazepoxide have ED50's of 26 μM and 200 μM, respectively, whereas the ED50 for glycine is 25 μM. The inhibitory effects of 10 of the agents in 2 other central nervous system membrane assays, for the opiate receptor and the muscarinic cholinergic receptor, do not correlate with any of the in vivo pharmalogic and behavioral tests. The benzodiazepine derivatives may exert their antianxiety, antoconvulsant and muscle relaxant effects by mimicking the effects of the neurotransmitter glycine at its central nervous system receptor sites.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1974|
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