Szczawińska K, Cenajek-Musiał D, Nowakowska E, Chodera A
Department of Pharmacology, Academy of Medicine, Poznań, Poland.
Eur J Pharmacol. 1988 Feb 16;147(1):7-11. doi: 10.1016/0014-2999(88)90627-9.
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.
开展了多项研究，以评估[3H]氟硝西泮与大鼠大脑皮质细胞膜的结合情况。这些大鼠通过每天腹腔注射硝西泮，分别对硝西泮的抗焦虑和镇静作用（14天后）以及抗惊厥作用（电休克，28天后）产生耐受性。仅在对抗惊厥作用产生耐受性的组中发现特异性[3H]氟硝西泮结合位点的数量显著减少。对奥沙西泮也进行了相同的实验。由于没有耐受性迹象，每天腹腔注射10mg/kg的该药物，持续6周。未出现耐受性，且[3H]氟硝西泮结合位点密度没有变化。我们得出结论，对硝西泮抗惊厥作用的耐受性可能与苯二氮䓬受体的下调有关。
