Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction

The direct effects of alinidine (N-allyl-clonidine) on the sinus node and atrioventricular (AV) junction were studied in 18 anesthetized dogs. Stimulus frequency-response curves to right stellate ganglion and right cervical vagus stimulations as well as responses to norepinephrine or acetylcholine were determined before and after selective perfusion of alinidine into the sinus node artery. Alinidine (1 microgram/ml) had no effect on spontaneous sinus rate [148 +/- 5 (SE) beats/min]. However, alinidine concentrations of 5, 10, and 25 micrograms/ml produced significant (P less than 0.05) sinus slowing to 138, 127, and 121 beats/min, respectively. Recovery to control rate was dose dependent and took from 4 to 33 min. Sinus rate increases with right stellate stimulations were not affected by alinidine. However, sinus rate decreases with right vagal stimulations were significantly (P less than 0.01) attenuated by alinidine. The negative chronotropic effects of acetylcholine were not influenced by alinidine. Alinidine (1-100 micrograms/ml into AV node artery) had no effect on the A-H interval of the His bundle electrogram. However, alinidine (10 and 25 micrograms/ml) diminished the AV block produced by stimulation of the left vagus in electrically paced hearts but not the negative dromotropic actions of directly administered acetylcholine. Thus alinidine has direct negative chronotropic effects, no effect on sinus node responses to sympathetic stimulation, ability to diminish sinus node and AV junctional responses to vagal stimulations without interference at the cholinergic muscarinic receptor, and 4) no effect on AV nodal conduction.