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Decrease in [3H]flunitrazepam receptor binding in rats tolerant to the effects of nitrazepam.

K Szczawińska·D Cenajek-Musiał·E Nowakowska·A Chodera
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Abstract

Studies were performed to evaluate the binding of [3H]flunitrazepam to cell membranes from the brain cortex of rats that were made tolerant, by the i.p. administration of nitrazepam once daily, to the anxiolytic and sedative effects (after 14 days) and the anticonvulsant action (electroshock, after 28 days) of nitrazepam. A significant decrease in the number of specific [3H]flunitrazepam binding sites was found only in the group that was tolerant to the anticonvulsant effect. The same experiments were also carried out with oxazepam. Since there were no signs of tolerance, the administration of the drug, 10 mg/kg once daily i.p., was continued for 6 weeks. No tolerance occurred and there were no changes in [3H]flunitrazepam binding site density. We conclude that tolerance to the anticonvulsant effect of nitrazepam could be related to the down-regulation of the benzodiazepine receptors.

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AnimalsCerebral CortexDrug ToleranceFlunitrazepamIn Vitro TechniquesInjections, IntraperitonealMaleMembranesNitrazepamOxazepamRatsRats, Inbred StrainsReceptors, GABA-AJournal ArticleResearch Support, Non-U.S. Gov't

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K Szczawińska, D Cenajek-Musiał, E Nowakowska, A Chodera. 1988-02-16. Decrease in [3H]flunitrazepam receptor binding in rats tolerant to the effects of nitrazepam.. https://doi.org/10.1016/0014-2999(88)90627-9

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