[Effects of the dynorphin derivative "E2078" on hemodynamics and plasma catecholamines in dogs]

Recently, a dynorphin derivative (E2078) is synthesized as a kappa-agonist. Unlike dynorphin, E2078 is easily inactivated by peptidases. In this study, hemodynamic effects of E2078 were investigated in 54 adult mongrel dogs under enflurane anesthesia. They were divided into 6 groups according to the dose of E2078 administrated. In the small dosage groups (0.05, 0.1 mg.kg-1), systemic blood pressure was reduced due to cardiac depression. In the large dosage groups (1.0 mg.kg-1, 10 mg.kg-1), the systemic blood pressure decreased due to vasodilation while the cardiac output increased. In the 1.0 mg.kg-1 group, the heart rate decreased, but it increased in the 10 mg.kg-1 group. This difference could be caused by decreased plasma catecholamines in the 1.0 mg.kg-1 group, and their increase in the 10 mg.kg-1 group. The changes in plasma catecholamine levels might be a factor contributing to circulatory depression due to decreased norepinephrine release from the sympathetic nerve endings by E2078 as observed following administration of other kappa-ligands. Another factor for hemodynamic depression would be a direct action of E2078 to dilate vascular bed.