Hoffman W E, Feld J M, Larscheid P, Cook J M, Albrecht R F, Miletich D J
Eur J Pharmacol. 1984 Nov 27;106(3):585-91. doi: 10.1016/0014-2999(84)90062-1.
There is a need in clinical practice for an antagonist which can reverse the sedative action of benzodiazepines. Recently, 3-hydroxymethyl-beta-carboline (3-HMC) has been reported to inhibit the sleep inducing effects of flurazepam. The effects of flurazepam (0.5, 5 and 50 mg/kg) on cerebral blood flow (CBF) and cerebral O2 consumption (CMRO2) were evaluated in rats and the ability of 3-HMC to reverse these changes was determined. Regional CBF was measured with radioactive microspheres and cortical CMRO2 was calculated from sagittal sinus-arterial O2 content differences and cortical CBF. Flurazepam produced dose dependent decreases in CBF and CMRO2 which were significant at 5 and 50 mg/kg. 3-HMC (5 mg/kg) inhibited flurazepam induced changes at the 5 mg/kg dose but had little effect on the CBF and CMRO2 depression produced by 50 mg/kg flurazepam. At a dose of 25 mg/kg, 3-HMC inhibited the effects of both 5 and 50 mg/kg flurazepam. Blood pressure and heart rate were also decreased by flurazepam but these variables were not reversed as effectively by 3-HMC treatment. The results indicate that 3-HMC is an active antagonist of the cerebrovascular and cerebral metabolic depression produced by flurazepam and can stimulate CBF and CMRO2 at high doses when given alone.
临床实践中需要一种能逆转苯二氮䓬类药物镇静作用的拮抗剂。最近，有报道称3 - 羟甲基 - β - 咔啉（3 - HMC）可抑制氟西泮的助眠作用。本研究评估了氟西泮（0.5、5和50 mg/kg）对大鼠脑血流量（CBF）和脑氧耗量（CMRO2）的影响，并测定了3 - HMC逆转这些变化的能力。采用放射性微球测量局部脑血流量，并根据矢状窦 - 动脉血氧含量差异和皮质脑血流量计算皮质CMRO2。氟西泮可使CBF和CMRO2呈剂量依赖性降低，在5和50 mg/kg时具有显著意义。3 - HMC（5 mg/kg）可抑制5 mg/kg剂量氟西泮引起的变化，但对50 mg/kg氟西泮引起的CBF和CMRO2降低作用甚微。在25 mg/kg剂量时，3 - HMC可抑制5和50 mg/kg氟西泮的作用。氟西泮还可使血压和心率降低，但3 - HMC治疗对这些变量的逆转效果不佳。结果表明，3 - HMC是氟西泮引起的脑血管和脑代谢抑制的有效拮抗剂，单独给予高剂量时可刺激CBF和CMRO2。
