分子和神经化学的影响评估etizolam GABAA受体在正常和压力条件。

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桑娜E,保罗D, Tuveri F, F马萨,Maciocco E,水C, Floris C,丰塔纳SN,玛丽亚G, Biggio G

分子和神经化学的影响评估etizolam GABAA受体在正常和压力条件。

Arzneimittelforschung。1999年2月,49 (2):88 - 95。

PubMed ID

10083975 (在PubMed

]

文摘

thienobenzodiazepine导数etizolam(中科院40054-69-1,6 - (o-chlorophenyl) 8-ethyl-1-methyl-4h-s-triazolo(上)thienol (1,4) diazepine)是一种有效的抗焦虑药的药理相似古典苯二氮卓类。为了理顺etizolam的治疗用途,其药效学特性对GABAA受体研究的比较研究与其他配体对人类重组GABAA和老鼠大脑受体。Etizolam抑制浓度的方式[3 h] flunitrazepam (ca 1622-62-4)绑定到鼠皮层膜,4.5 nmol / l的亲和力比阿普唑仑(ca 28981-97-7) (7.9 nmol / l)。Ethizolam增强GABA-induced Cl -电流对GABAA受体卵母细胞表达人类克隆。与α1β2γ2 s亚基组合,etizolam产生GABA-induced电流增加73%的EC50 92 nmol / l。在同一受体类型、阿普唑仑表现出更高程度的增强作用和效力(98%,EC50 56 nmol / l)。α2β2γ2 s或α3β2γ2 s亚基结构,etizolam的影响类似于阿普唑仑。Flumazenil (ca 78755-81-4)完全阻塞etizolam和阿普唑仑对GABA-induced电流的影响。Etizolam i.p管理。在改变对其行体外t - 35 [s] butylbicyclophosphorothionate (35 [s] tbps)绑定到老鼠大脑皮层,而阿普唑仑和abecarnil (ca 111841-85-1)显著降低该参数。 However, etizolam similarly to abecarnil and alprazolam, antagonized isoniazid-induced increase (61%) in [35S]-TBPS binding to rat cortical membranes. Further, etizolam inhibited in a dose-dependent manner basal acetylcholine release from both hippocampus and prefrontal cortex, and reversed foot-shock-induced increase of basal acetylcholine release to a control level. Altogether, these results suggest that etizolam may have a reduced intrinsic activity, at least at specific subpopulations of GABAA receptors. This property, together with the pharmacokinetic indication of a short-acting drug, may characterize etizolam as a ligand endowed with less side-effects typical of full agonits such as diazepam (CAS 439-14-5) and alprazolam. Finally, given its marked efficacy under conditions of GABAergic deficit, etizolam may represent a possible drug of choice with reduced liability to produce tolerance and dependence after long-term treatment of anxiety and stress syndromes.

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药物

Etizolam