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Studies on active transport of (E)-10-hydroxynortriptyline in the kidney and brain of rats: effects of propranolol and quinidine.
- Source :
-
Pharmacology & toxicology [Pharmacol Toxicol] 1991 May; Vol. 68 (5), pp. 380-3. - Publication Year :
- 1991
-
Abstract
- 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.
- Subjects :
- Animals
Biological Transport, Active drug effects
Brain metabolism
Disease Models, Animal
Kidney metabolism
Male
Metabolic Clearance Rate drug effects
Nortriptyline pharmacokinetics
Rats
Rats, Inbred Strains
Brain drug effects
Kidney drug effects
Nortriptyline analogs & derivatives
Propranolol pharmacology
Quinidine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0901-9928
- Volume :
- 68
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 1946183
- Full Text :
- https://doi.org/10.1111/j.1600-0773.1991.tb01256.x