Blockade of biochemical and physiological responses of cardiac muscle to norepinephrine by N-tert.-butylmethoxamine (butoxamine).
Blockade of biochemical and physiological responses of cardiac muscle to norepinephrine by N-tert.-butylmethoxamine (butoxamine).
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N-叔丁基甲氧胺（丁氧胺）阻断心肌对去甲肾上腺素的生化和生理反应。
DOI：
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发表时间：
1972
影响因子：
3.5
通讯作者：
S. Mayer
中科院分区：
文献类型：
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作者：
W. Wastila;J. Su;W. Friedman;S. Mayer
甲氧胺同类物被描述为β 2肾上腺素能阻滞剂，对心脏肾上腺素能反应几乎没有影响，并且还被描述为具有阻滞心脏腺苷39，59-单磷酸（环AMP）的形成的能力，但不具有响应于去甲肾上腺素的收缩力。本实验的目的是评价N-叔丁基-N-甲基-N-乙基-N-甲基-N-乙基-N-甲基-N丁甲氧胺（丁氧胺）作为心脏肾上腺素能阻滞剂在体内和体外。对开胸麻醉犬给予去甲肾上腺素（1 µg/kg）后，在7至10秒内使心脏cAMP增加2倍。其先于右心室收缩力的增加（15秒内2.4倍）和磷酸化酶A的形成（15秒内13倍）。丁恶胺（2.5-15 µg/kg iv.）产生了剂量依赖性的磷酸化酶a形成的阻滞; 10 mg/kg减少了三分之二的收缩，磷酸化酶和环AMP反应去甲肾上腺素。单独使用丁氧胺可降低收缩力和环磷酸腺苷含量。重复给予去甲肾上腺素可逆转收缩力和磷酸化酶的阻滞。去甲肾上腺素对猫离体乳头肌等长张力的增强作用可被3 × 10 - 5 M丁恶胺竞争性阻断。去甲肾上腺素的EC 50从4 × 10 - 7 M增加到3 × 10 - 6 M。对猫离体右心房的变时作用以半竞争性方式被阻断。单独的丁氧胺（> 3 × 10 - 5 M）降低了这两个参数。我们的结论是，虽然丁恶胺是一个相对较弱的拮抗剂，它阻止了肾上腺素能刺激的生化和生理心脏反应，并没有解离环AMP的形成从收缩力的增强。
Methoxamine congeners have been described as beta 2 adrenergic blocking agents with little effect on cardiac adrenergic responses and also as having the capacity to block the formation of cardiac adenosine 39, 59-monophosphate (cyclic AMP) but not contractile force in response to norepinephrine. The purpose of the present experiments was to evaluate the effectiveness of N- tert .-butylmethoxamine (butoxamine) as a cardiac adrenergic blocking agent in vivo and in vitro . Norepinephrine (1 µg/kg) administered to open-chest anesthetized dogs increased cardiac cyclic AMP 2-fold in 7 to 10 seconds. which preceded the increase in right ventricular contractile force (2.4-fold in 15 seconds) and formation of phosphorylase a (13-fold in 15 seconds). Butoxamine (2.5-15 µg/kg iv.) produced a dose-dependent blockade of phosphorylase a formation; 10 mg/kg reduced the contractile, phosphorylase and cyclic AMP responses to norepinephrine by two-thirds. Butoxamine alone depressed contractile force and cyclic AMP content. Repeated administration of norepinephrine reversed the blockade of contractile force and phosphorylase. Augmentation of isometric tension of isolated cat papillary muscles by norepinephrine was blocked competitively by 3 x 10 -5 M butoxamine. The EC50 of norepinephrine was increased from 4 x 10 -7 M to 3 x 10 -6 M. The chronotropic effect on cat isolated right atria was blocked in what appeared to be a semicompetitive fashion. Butoxamine alone (> 3 x 10 -5 M) depressed both parameters. We conclude that while butoxamine is a relatively weak antagonist, it blocks biochemical and physiological cardiac responses to adrenergic stimulation and does not dissociate cyclic AMP formation from augmentation of contractile force.