AF150(S) - A NEW FUNCTIONALLY SELECTIVE M(1) AGONIST IMPROVES COGNITIVE PERFORMANCE IN RATS
AF150(S) - A NEW FUNCTIONALLY SELECTIVE M(1) AGONIST IMPROVES COGNITIVE PERFORMANCE IN RATS
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DOI：
10.1016/0091-3057(94)00435-l
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发表时间：
1995-08-01
影响因子：
3.6
通讯作者：
FISHER, A
中科院分区：
文献类型：
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作者：
BRANDEIS, R;SAPIR, M;FISHER, A
本研究旨在评价一种新的功能选择性部分M（1）激动剂AF 150（S）逆转大鼠认知障碍的能力。使用涉及双侧ICV注射AF 64 A（3 nmol/2 μ l/侧）的记忆缺陷诱导的动物模型。AF 150（S）经口给药。建立了该化合物的药效学特征，并评价了其一般毒性。采用避暗被动回避、Morris水迷宫参考记忆和桡臂迷宫工作记忆三种行为任务进行测试。AF 150（S）的无符号剂量为> 40 mg/kg，而LD（50）为> 500 mg/kg。相比之下，逆转各种任务表现障碍的有效剂量要低得多（0.5-5 mg/kg）。数据表明，AF 150（S）具有潜在的认知增强能力，可能是由于胆碱能功能的特异性增加。
This study was aimed at evaluating the ability of a new functionally selective partial M(1) agonist, AF150(S), to reverse cognitive impairments in rats. A memory deficits-induced animal model was used that involved AF64A (3 nmol/2 mu l/side) bilaterally injected ICV. AF150(S) was administered PO. The pharmacodynamic profile of the compound was established and its general toxicity was evaluated. Animals were tested on three behavioral tasks: step-through passive avoidance, Morris water maze reference memory paradigm, and radial arm maze working memory paradigm. The sign-free dose of AF150(S) was > 40 mg/kg whereas the LD(50) was > 500 mg/kg. In comparison, the effective dose in reversing performance impairments on the various tasks was much lower (0.5-5 mg/kg). The data suggest that AF150(S) possesses potential cognitive enhancement abilities, probably due to a specific increase of cholinergic function.