Anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319.
Anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319.
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不对称双季铵盐 6-氨基喹啉盐 NSC-176319 的抗胆碱酯酶活性。
DOI：
10.1016/0006-2952(82)90174-5
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发表时间：
1982
影响因子：
5.8
通讯作者：
Unwin,S
中科院分区：
文献类型：
--
作者：
Hacker,MP;Braddock,J;Unwin,S
本文研究了非对称双季铵盐6-氨基喹啉盐NSC-176319(QB)的体外抗胆碱酯酶活性。结果表明，QB对乙酰胆碱酯酶(或真胆碱酯酶)和丁基胆碱酯酶(或假性胆碱酯酶)均具有非竞争性抑制作用，对乙酰胆碱酯酶和丁酰胆碱酯酶的AK1分别为0.50×10~6−6M和1.5×10~6−M。此外，QB以非竞争性方式抑制小鼠血浆中的酯酶活性(Ki=4.2×10−6M)。这种抑制作用在开始时是瞬间的，并且不会随着药物和酶的孵育时间的延长而减弱。静脉注射QB 2 mg/kg的小鼠均在5分钟内死亡。在死亡之前，小鼠会出现严重的副交感神经症状和惊厥。虽然硫酸阿托品可减弱拟副交感神经的作用，但只有巴比妥酸盐麻醉才能预防死亡。
The anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319 (QB) was studiedin vitro.QB proved to be a noncompetitive inhibitor of both acetylcholinesterase (or true cholinesterase) and butyrylcholinesterase (or pseudocholinesterase) having aK1= 0.5 × 10−6M for acetylcholinesterase and 1.5 × 106−M for butyrylcholinesterase. Further, QB inhibited esterase activity of murine plasma in a noncompetitive manner (Ki= 4.2 × 10−6M). The inhibition was instantaneous in onset and did not diminish with prolonged incubation of the drug and enzyme. All mice treated intravenously with 2 mg QB/kg died within 5 min. Prior to death, mice developed severe parasympathomimetic effects and convulsions. Although the parasympathomimetic effects were diminished by atropine sulfate pretreatment, death could only be prevented by barbiturate anesthesia.