Effects of DJ-7141, a new alpha-2 agonist, 2-(2-chloro-6-fluorophenyl)-2,3,5,6-tetra-hydro-1H-imidazo[1,2-a] imidazole hydrochloride, on the isolated atrium, cross-perfused with blood from a support dog.

The effects of DJ-7141, a new alpha-2 agonist, on an isolated atrial preparation cross-perfused with arterial blood from a support dog were investigated. In the isolated atrium, a selective injection of DJ-7141 (1-100 micrograms) into the sinus node artery induced dose-dependent positive chronotropic and inotropic effects. The positive cardiac effects of DJ-7141 were not only inhibited by propranolol and by imipramine, but reversed to negative effects, whereas the positive cardiac effects of norepinephrine were blocked by propranolol and potentiated by imipramine. Tetrodotoxin (TTX) did not modify the cardiac responses to DJ-7141. After propranolol treatment, the negative chronotropic and inotropic responses to DJ-7141 were not influenced by atropine, which completely blocked acetylcholine-induced cardiac responses. When DJ-7141 was injected into the support dog at a dose of 10-300 micrograms/Kg i.v., it induced a brief increase in femoral arterial blood pressure and a long-lasting decrease in heart rate in the support dog and increases in atrial rate and contractile force in the isolated atrium. These results suggest that the new alpha-2 agonist, DJ-7141, induces indirect positive chronotropic and inotropic effects due to a tyramine-like action and direct negative cardiac effects in the isolated dog heart, and that the tyramine-like effect may be partially responsible for the increase in blood pressure seen with DJ-7141 in in situ dogs.