Lopez F, Miller L G, Greenblatt D J, Paul S M, Shader R I
Department of Medicine, LSU Medical Center, New Orleans, LA.
Pharmacol Biochem Behav. 1988 Jun;30(2):511-3. doi: 10.1016/0091-3057(88)90488-1.
The triazolobenzodiazepine alprazolam appears to have a unique clinical spectrum, and recent studies indicate unusual binding properties at the benzodiazepine receptor when assessed in vivo at low doses (0.02-0.05 mg/kg). To assess the behavioral activity of alprazolam at low doses, we examined open-field activity after one hour in mice treated with alprazolam, triazolam, and clonazepam. Following triazolam and clonazepam administration, open-field activity decreased in a dose-dependent fashion. In contrast, low doses of alprazolam resulted in an increase in open-field activity, whereas higher doses decreased activity. For all three drugs, activity was linearly related to receptor binding. Pretreatment with a dose of the benzodiazepine antagonist Ro15-1788 sufficient to fully occupy receptors had no effect on open-field activity, but when administered concurrently with alprazolam (0.05 mg/kg) prevented the increase in activity seen with alprazolam alone. Increased open-field motor activity represents a behavioral correlate to the increases in receptor binding seen with low-doses of alprazolam. Changes in activity appear to be mediated at the benzodiazepine receptor, since an antagonist prevents increased activity. These data suggest that the unique clinical effects of alprazolam may be due in part to unusual interactions with the benzodiazepine receptor.
三唑并苯二氮䓬类药物阿普唑仑似乎具有独特的临床谱，最近的研究表明，在低剂量（0.02 - 0.05毫克/千克）体内评估时，它在苯二氮䓬受体上具有不寻常的结合特性。为了评估阿普唑仑低剂量时的行为活性，我们检测了用阿普唑仑、三唑仑和氯硝西泮处理的小鼠在一小时后的旷场活动。给予三唑仑和氯硝西泮后，旷场活动呈剂量依赖性降低。相比之下，低剂量的阿普唑仑会导致旷场活动增加，而高剂量则会降低活动。对于所有三种药物，活性与受体结合呈线性相关。用足以完全占据受体的剂量的苯二氮䓬拮抗剂Ro15 - 1788预处理对旷场活动没有影响，但与阿普唑仑（0.05毫克/千克）同时给药时，可阻止单独使用阿普唑仑时出现的活动增加。旷场运动活动增加代表了与低剂量阿普唑仑引起的受体结合增加相关的行为表现。活动变化似乎是在苯二氮䓬受体介导的，因为拮抗剂可阻止活动增加。这些数据表明，阿普唑仑独特的临床效果可能部分归因于与苯二氮䓬受体的异常相互作用。
