Studies on active transport of (E)-10-hydroxynortriptyline in the kidney and brain of rats: effects of propranolol and quinidine.
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.
Otani
K
K
Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
Kaneko
S
S
Bertilsson
L
L
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009661:Nortriptyline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011433:Propranolol / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
C013567:10-hydroxynortriptyline; D011433:Propranolol; D009661:Nortriptyline; D011802:Quinidine