Hoffman W E, Albrecht R F, Miletich D J, Hagen T J, Cook J M
Anesth Analg. 1986 Jun;65(6):639-44.
Physostigmine has been reported to reverse the sedation and paradoxical delirium induced by benzodiazepines. Little is known about how these drugs may interact to produce changes in cerebral metabolism and cerebral blood flow (CBF). In the present experiments, the effect of physostigmine on cerebral oxygen consumption (CMRO2) and CBF as well as the ability of physostigmine to reverse the effects of midazolam and 3-carbo-t-butoxy-B-carboline (B-CCT), a benzodiazepine antagonist, was tested in rats. Physostigmine by itself produced dose-dependent increases in blood pressure, CBF, and CMRO2, and it inhibited the decrease in these parameters produced by midazolam. Alone, B-CCT increased CBF and CMRO2, and these changes were potentiated by physostigmine. Thus, physostigmine increases CBF and CMRO2, probably by a direct effect on central cholinergic pathways. The ability of physostigmine to antagonize the metabolic effects of midazolam and to potentiate the stimulation produced by B-CCT suggests an additive effect of the two neurotransmitter systems rather than a direct interaction at the central receptor sites.
据报道，毒扁豆碱可逆转苯二氮䓬类药物引起的镇静作用和反常谵妄。关于这些药物如何相互作用以引起脑代谢和脑血流量（CBF）的变化，目前知之甚少。在本实验中，在大鼠身上测试了毒扁豆碱对脑氧耗量（CMRO2）和CBF的影响，以及毒扁豆碱逆转咪达唑仑和苯二氮䓬类拮抗剂3-羧基叔丁氧基-β-咔啉（B-CCT）作用的能力。毒扁豆碱本身可使血压、CBF和CMRO2呈剂量依赖性增加，并抑制咪达唑仑引起的这些参数的降低。单独使用时，B-CCT可增加CBF和CMRO2，而毒扁豆碱可增强这些变化。因此，毒扁豆碱可能通过直接作用于中枢胆碱能通路来增加CBF和CMRO2。毒扁豆碱拮抗咪达唑仑代谢作用并增强B-CCT产生的刺激作用的能力表明，这两种神经递质系统具有相加作用，而非在中枢受体部位直接相互作用。
