Upton R N, Martinez A M, Grant C
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
Br J Anaesth. 2009 Dec;103(6):848-57. doi: 10.1093/bja/aep269. Epub 2009 Sep 29.
CNS 7056 is an esterase-metabolized benzodiazepine sedative currently under development. Its short duration of action would suggest a clinical role similar to midazolam or propofol.
The effect of a range of doses of CNS 7056, midazolam, and propofol on depth of sedation, the respiratory system, and the cardiovascular system was studied in chronically instrumented sheep (n=5 or 6). The low, medium, and high doses of CNS 7056, midazolam, and propofol were 0.37, 0.74, and 1.47 mg kg(-1); 0.05, 0.1, and 0.2 mg kg(-1); and 1, 2, and 4 mg kg(-1), respectively.
CNS 7056 produced substantial sedation with rapid onset and offset for all doses, with duration rather than depth of sedation increasing with the dose. The lower doses of midazolam had minimal sedative effect; increasing the dose produced variable but longer term sedation. Sedation from propofol was comparable with that of CNS 7056 for the medium and high doses only. The high doses produced approximately 20 min of sedation. All three drugs produced dose-dependent respiratory (e.g. reductions in arterial oxygen tension) and cardiovascular depression (e.g. reductions in mean arterial pressure). For CNS 7056, midazolam, and propofol, the magnitude of the cardiovascular and respiratory depression was proportional to the depth of sedation achieved for any given drug or dose. For all three drugs, the respiratory and cardiovascular depression was not of sufficient magnitude to endanger the animals.
CNS 7056 is a powerful and short-acting anaesthetic in sheep with respiratory and cardiovascular effects consistent with its sedative/anaesthetic qualities.
CNS 7056是一种正在研发的经酯酶代谢的苯二氮䓬类镇静剂。其作用持续时间短，表明其临床作用类似于咪达唑仑或丙泊酚。
在长期植入监测设备的绵羊（n = 5或6）中，研究了一系列剂量的CNS 7056、咪达唑仑和丙泊酚对镇静深度、呼吸系统和心血管系统的影响。CNS 7056、咪达唑仑和丙泊酚的低、中、高剂量分别为0.37、0.74和1.47 mg·kg⁻¹；0.05、0.1和0.2 mg·kg⁻¹；以及1、2和4 mg·kg⁻¹。
CNS 7056在所有剂量下均能产生显著的镇静作用，起效快且作用消失快，镇静持续时间而非深度随剂量增加而延长。较低剂量的咪达唑仑镇静作用极小；增加剂量会产生可变但更持久的镇静作用。丙泊酚仅在中、高剂量时的镇静作用与CNS 7056相当。高剂量可产生约20分钟的镇静作用。所有三种药物均产生剂量依赖性的呼吸抑制（如动脉血氧张力降低）和心血管抑制（如平均动脉压降低）。对于CNS 7056、咪达唑仑和丙泊酚，心血管和呼吸抑制的程度与任何给定药物或剂量所达到的镇静深度成正比。对于所有三种药物，呼吸和心血管抑制的程度均不足以危及动物生命。
CNS 7056在绵羊中是一种强效短效麻醉剂，其对呼吸和心血管系统的影响与其镇静/麻醉特性一致。
