Effect of autonomic blocking agents on chronotropic actions of 1-alpha-acetylmethadol.

The objective of this investigation was to determine whether or not autonomic receptors are involved in the chronotropic responses to 1-alpha-acetylmethadol (LAAM) and congeners (1-alpha-acetylnormethadol, norLAAM; 1-alpha-acetyldinormethadol, dinorLAAM). The effects of atropine were studied in vitro using isolated guinea-pig right atria and in vivo in anesthetized dogs. The effect of d,l-propranolol, a beta-adrenergic receptor blocking agent was studied in vitro only. Atropine attenuated, but did not block completely, the negative chronotropic responses to the narcotic agonists. Propranolol blocked completely the positive chronotropic response to norLAAM and appeared to increase the negative chronotropic response to dinorLAAM. It is concluded that: 1) muscarinic cholinergic receptors play a role in the negative chronotropic response; 2) the positive chronotropic response to norLAAM involves activation of beta-adrenergic receptors.