RU33368（一种对神经元苯二氮䓬受体具有低亲和力的配体）对啮齿动物行为及大鼠小脑切片中γ-氨基丁酸介导的突触传递的影响。

Effects of RU33368, a low affinity ligand for neuronal benzodiazepine receptors, on rodent behaviours and GABA-mediated synaptic transmission in rat cerebellar slices.

Gardner C R, Ward R A, Deacon R M, Bagust J, Walker R J

Roussel Laboratories Ltd, Covingham, Swindon, U.K.

Gen Pharmacol. 1992 Nov;23(6):1193-8. doi: 10.1016/0306-3623(92)90311-7.

Abstract

The effects of the low affinity benzodiazepine receptor ligand RU33368 were studied on rodent behaviours and on GABA-mediated synaptic transmission in rat cerebellar slices. 2. RU33368 inhibited stress induced ultrasounds in rat pups without inducing marked muscle relaxation. RU33368 also enhanced operant responding in rats that had been suppressed by mild footshock. These effects of RU33368 in these two models of anxiety were both blocked by the benzodiazepine antagonist Ro15-1788 (flumazonil). 3. In cerebellar slices RU33368 enhanced stimulus-induced synaptic inhibition of Purkinje layer cells with a minimal effective concentration in the order of 1 microM. The classical benzodiazepine agonist RU32007 was approx. 10 times more potent. This action of RU33368 was blocked by Ro15-1788. 4. The minimal effective concentration of RU33368 fully blocked the effect of RU32007 in 2 of 4 cells tested and partially antagonized it in a third cell. 5. These data suggest that RU33368 is a partial agonist at benzodiazepine receptors and this, at least in part, explains its non-sedative anxiolytic behavioural profile.

摘要

研究了低亲和力苯二氮䓬受体配体RU33368对啮齿动物行为以及大鼠小脑切片中γ-氨基丁酸（GABA）介导的突触传递的影响。2. RU33368可抑制幼鼠应激诱导的超声发声，且不会引起明显的肌肉松弛。RU33368还增强了因轻度足部电击而受到抑制的大鼠的操作性反应。在这两种焦虑模型中，RU33368的这些作用均被苯二氮䓬拮抗剂Ro15 - 1788（氟马西尼）阻断。3. 在小脑切片中，RU33368增强了对浦肯野层细胞的刺激诱导的突触抑制，其最小有效浓度约为1微摩尔。经典的苯二氮䓬激动剂RU32007的效力约强10倍。RU33368的这一作用被Ro15 - 1788阻断。4. RU33368的最小有效浓度在4个测试细胞中的2个中完全阻断了RU32007的作用，并在第三个细胞中部分拮抗了其作用。5. 这些数据表明，RU33368是苯二氮䓬受体的部分激动剂，这至少在一定程度上解释了其非镇静性抗焦虑的行为特征。