Nutt D J, Glue P, Lawson C, Wilson S
Reckitt & Colman Psychopharmacology Unit, School of Medical Sciences, Bristol, United Kingdom.
Arch Gen Psychiatry. 1990 Oct;47(10):917-25. doi: 10.1001/archpsyc.1990.01810220033004.
The possibility that panic disorder might be due to abnormal activity of endogenous ligands of the benzodiazepine receptor was investigated with the use of the benzodiazepine antagonist flumazenil. Physiological and subjective psychological responses to this selective antagonist were measured in 10 patients with panic disorder and in 10 control subjects, by using a placebo-controlled crossover study design. Subjective anxiety responses after flumazenil infusion were significantly higher in the patient group with panic disorder than in the controls, and eight patients with panic disorder but no controls had panic attacks. This anxiogenic effect of flumazenil in the patients argues against the presence of endogenous anxiogenic (inverse agonist) ligands. Possible explanations include the differential production of an anxiolytic endogenous ligand or an altered benzodiazepine receptor "set-point." Such an abnormality may contribute to the pathogenesis of panic disorder.
使用苯二氮䓬拮抗剂氟马西尼，研究惊恐障碍可能是由于苯二氮䓬受体内源性配体的异常活性所致。采用安慰剂对照交叉研究设计，对10例惊恐障碍患者和10例对照者测量了对这种选择性拮抗剂的生理和主观心理反应。氟马西尼输注后，惊恐障碍患者组的主观焦虑反应显著高于对照组，8例惊恐障碍患者出现惊恐发作，而对照组无此情况。氟马西尼对患者的这种致焦虑作用与内源性致焦虑（反向激动剂）配体的存在相悖。可能的解释包括抗焦虑内源性配体的差异产生或苯二氮䓬受体“设定点”的改变。这种异常可能有助于惊恐障碍的发病机制。
