Differential hemodynamic, metabolic and hormonal effects of morphine and morphine-6-glucuronide

Although the hyperglycemic effect of morphine has been previously described, it is not clear whether this is the result of increased glucose production and/or decreased glucose utilization and if this metabolic effect is lost with glucuronidation. This study assessed the hemodynamic (heart rate; HR and mean arterial blood pressure; MABP), hormonal and whole body glucose metabolic effects of morphine (MOR) and its metabolite morphine 6-glucuronide (MOR-6G) in conscious unrestrained chronically catheterized rats. Whole body glucose kinetics were assessed with a primed constant intravenous infusion of [3-3H]glucose in rats infused i.c.v. with H2O (Con; 5 microliters/h), MOR (80 micrograms/h) or MOR-6G (1 microgram/h) for a total of 4 h. MOR administration resulted in a significant 20% elevation in HR and no change in MABP. MOR-6G produced a 14% increase in HR and no change in MABP. A significant rise in plasma glucose (+23%), hepatic glucose production (Ra; +27-61%) and whole body glucose utilization (Rd; +31-61%) was also observed within 60 min of MOR administration. I.c.v. MOR-6G resulted in hyperglycemia (+60%), stimulation of glucose Ra (+60%) and glucose Rd (+50%). No significant alterations were noted in hemodynamic, metabolic and hormonal parameters of H2O infused rats. I.c.v. MOR resulted in a significant increases in epinephrine (2-fold), norepinephrine (50%), corticosterone (97%) with no alterations in plasma insulin and glucagon. I.c.v. MOR-6G resulted in more marked elevations in norepinephrine (5-fold), epinephrine (7-fold) and similar elevation in corticosterone (99%) and modest elevation of glucagon (40%).(ABSTRACT TRUNCATED AT 250 WORDS)