10-hydroxynortriptyline and Disease-Models--Animal

Studies in humans have given strong support of an active transport of (E)-10-hydroxynortriptyline [E)-10-OH-NT) in the kidney and from the cerebrospinal fluid. After 3 days of intraperitoneal injections of (E)-10-OH-NT (10 mg/kg t.i.d.) in a rat model, we investigated the effect of propranolol and quinidine (25 and 2.5 mg/kg injected 6 times during day 3) on the concentrations of (E)-10-OH-NT in urine, plasma (total and unbound) and brain. In a group of control rats the renal clearance of (E)-10-OH-NT varied 10-fold between rats, but was reproducible from Day 2 to Day 3 (r = 0.83; n = 8; p less than 0.05). Quinidine markedly decreased the renal clearance of both total and unbound (E)-10-OH-NT from plasma, while the effect of propranolol was less pronounced. There was no difference in the ratio of (E)-10-OH-NT concentrations in brain and plasma (unbound) between treated and control rats. We conclude that (E)-10-OH-NT is actively secreted in the rat proximal tubule and that the activity of this system varies between rats, but is constant in the individual rat. Quinidine, and to a less extent propranolol, inhibits this renal secretion. By the present methodology we could not demonstrate an active transport of (E)-10-OH-NT from brain to blood in the rat. Studies using other methods are needed to further elucidate this.

Topics: Animals; Biological Transport, Active; Brain; Disease Models, Animal; Kidney; Male; Metabolic Clearance Rate; Nortriptyline; Propranolol; Quinidine; Rats; Rats, Inbred Strains