Cardiac and autonomic nervous system effects of L-alphacetylmethadol (LAAM)

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.