Miller D W, Yourick D L, Tessel R E
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
Eur J Pharmacol. 1989 Nov 28;173(1):1-10. doi: 10.1016/0014-2999(89)90002-2.
Injection of the partial benzodiazepine inverse agonist Ro15-4513 (1-32 mg/kg i.p.) or nonconvulsant i.v. doses of the full benzodiazepine inverse agonist beta-CCE immediately following cessation of exposure of rats to an anesthetic concentration of methoxyflurane significantly antagonized the duration of methoxyflurane anesthesia as measured by recovery of the righting reflex and/or pain sensitivity. This antagonism was inhibited by the benzodiazepine antagonist Ro15-1788 at doses which alone did not alter the duration of methoxyflurane anesthesia. In addition, high-dose Ro15-4513 pretreatment (32 mg/kg) antagonized the induction and duration of methoxyflurane anesthesia but was unable to prevent methoxyflurane anesthesia or affect the induction or duration of anesthesia induced by the dissociative anesthetic ketamine (100 mg/kg). These findings indicate that methoxyflurane anesthesia can be selectively antagonized by the inverse agonistic action of Ro15-4513 and beta-CCE.
在大鼠停止暴露于麻醉浓度的甲氧氟烷后，立即腹腔注射部分苯二氮䓬反向激动剂Ro15 - 4513（1 - 32毫克/千克）或静脉注射非惊厥剂量的全苯二氮䓬反向激动剂β-CCE，通过翻正反射恢复和/或痛觉敏感性测量，可显著拮抗甲氧氟烷麻醉的持续时间。这种拮抗作用可被苯二氮䓬拮抗剂Ro15 - 1788抑制，该剂量单独使用时不会改变甲氧氟烷麻醉的持续时间。此外，高剂量Ro15 - 4513预处理（32毫克/千克）可拮抗甲氧氟烷麻醉的诱导和持续时间，但无法预防甲氧氟烷麻醉，也不影响解离麻醉剂氯胺酮（100毫克/千克）诱导的麻醉诱导或持续时间。这些发现表明，Ro15 - 4513和β-CCE的反向激动作用可选择性拮抗甲氧氟烷麻醉。
