Naughton N, Hoffman W E, Larscheid P, Cook J M, Albrecht R F, Miletich D J
Life Sci. 1985 Jun 10;36(23):2239-45. doi: 10.1016/0024-3205(85)90335-2.
It is reported that benzodiazepines such as diazepam will stimulate the opiate receptor system and that B-carboline drugs, which are benzodiazepine antagonists, may interact with opiate receptors directly. The ability of 3-hydroxymethyl-B-carboline (3-HMC) to antagonize several parameters of fentanyl anesthesia was tested here in rats. Fentanyl (25 and 100 micrograms/kg iv) produced dose dependent depression of cerebral blood flow (CBF), measured by radioactive microspheres, and cerebral oxygen consumption (CMRO2). These effects were significantly inhibited by 10 mg/kg 3-HMC iv. To test for the specificity of this effect, 3-HMC was also given to rats ventilated with inspire concentrations of 2% halothane. Halothane depressed CMRO2 equally in 3-HMC and vehicle treated rats, indicating no significant effect of the benzodiazepine antagonist. Blood pressure was increased in 3-HMC compared to vehicle treated animals during both fentanyl and halothane anesthesia. CBF was increased in 3-HMC vs vehicle treated rats during halothane anesthesia but this could be accounted for by the elevated blood pressure and lack of cerebral autoregulation rather than a direct cerebrovascular effect. 3-HMC decreased the sleep time and respiratory depressant effects of fentanyl but enhanced the analgesic effects of the opiate, as measured by time to respond to a hot plate stimulus. These results indicate that 3-HMC has the ability to specifically antagonize fentanyl anesthesia. These effects may be produced by an action of 3-HMC at the benzodiazepine receptor and/or by an action of the B-carboline at opioid receptors.
据报道，地西泮等苯二氮䓬类药物会刺激阿片受体系统，而作为苯二氮䓬拮抗剂的β-咔啉类药物可能直接与阿片受体相互作用。本文在大鼠中测试了3-羟甲基-β-咔啉（3-HMC）拮抗芬太尼麻醉若干参数的能力。通过放射性微球测量，芬太尼（静脉注射25和100微克/千克）产生剂量依赖性的脑血流量（CBF）降低以及脑氧耗量（CMRO2）降低。静脉注射10毫克/千克的3-HMC可显著抑制这些效应。为了测试这种效应的特异性，还对吸入2%氟烷浓度通气的大鼠给予3-HMC。在3-HMC处理组和溶剂处理组大鼠中，氟烷对CMRO2的抑制作用相同，表明苯二氮䓬拮抗剂无显著作用。在芬太尼和氟烷麻醉期间，与溶剂处理的动物相比，3-HMC处理组的血压升高。在氟烷麻醉期间，与溶剂处理组大鼠相比，3-HMC处理组的大鼠CBF升高，但这可能是由于血压升高和缺乏脑自动调节，而非直接的脑血管效应所致。3-HMC缩短了芬太尼的睡眠时间和呼吸抑制作用，但增强了阿片类药物的镇痛作用，这通过对热板刺激的反应时间来衡量。这些结果表明，3-HMC具有特异性拮抗芬太尼麻醉的能力。这些效应可能是由3-HMC在苯二氮䓬受体上的作用和/或β-咔啉在阿片受体上的作用产生的。
