Langley A E, Lehman T M, Kirlangitis J, Zeid R
Arch Int Pharmacodyn Ther. 1982 Oct;259(2):250-8.
The effects of 1-alphacetylmethadol (LAAM) on heart rate and force of contraction of isolated guinea-pig hearts and on release of tritium from sympathetic nerves were investigated. In vitro perfusion with LAAM depressed resting heart rate and right ventricular pressure. Nerve stimulation-induced tritium overflow was inhibited in a concentration related manner by LAAM. Increasing the calcium concentration in the perfusate partially inhibited the negative chronotropy and completely prevented the negative inotropic effect. One micromolar atropine prevented the negative chronotropy, partially inhibited the negative inotropic effect of LAAM and the depression of tritium release. Ten micromolar naltrexone failed to antagonize the effects of LAAM. Our results suggest that LAAM: 1) has a direct myocardial depressant effect which may be due to an inhibition of calcium influx; 2) produces a negative chronotropy through stimulation of atrial muscarinic receptors; and 3) interacts with presynaptic muscarinic receptors which modulate nerve stimulation-induced release of noradrenaline.
研究了1-α-乙酰美沙多（LAAM）对豚鼠离体心脏心率和收缩力以及对交感神经释放氚的影响。用LAAM进行体外灌注可降低静息心率和右心室压力。LAAM以浓度相关的方式抑制神经刺激诱导的氚溢出。增加灌注液中的钙浓度可部分抑制负性变时作用，并完全防止负性变力作用。1微摩尔阿托品可防止负性变时作用，部分抑制LAAM的负性变力作用和氚释放的抑制。10微摩尔纳曲酮未能拮抗LAAM的作用。我们的结果表明，LAAM：1）具有直接的心肌抑制作用，这可能是由于抑制钙内流；2）通过刺激心房毒蕈碱受体产生负性变时作用；3）与调节神经刺激诱导的去甲肾上腺素释放的突触前毒蕈碱受体相互作用。
