Clonidine distribution in the rat: temporal relationship between tissue levels and blood pressure response.

1. The time course of the distribution of clonidine (20 microgram/kg, i.v.) was determined in the rat by use of a sensitive and specific radioimmunoassay, and was compared with the hypotensive response following this dose. 2. Levels of clonidine were determined in tissues at 2 min, corresponding to the beginning of the hypotensive phase of the drug, and then at 10, 30 and 120 min during recovery of blood pressure to the pre-dose level. The peak tissue concentrations of clonidine were found at 2 min, after which they declined in a mono-exponential manner. The half-lives of clonidine in the various tissues were similar to the half-life of the recovery of blood pressure. 3. Regional variations in clonidine distribution in the brain were not very great; however, the half-life was longer in the corpus striatum and shorter in the cerebellum than in other brain regions. 4. Clonidine concentrations were highest in the kidney and similarly distributed between the cortex and medulla. Concentrations of the drug in other tissues approximated those in brain. 5. Although clonidine is thought to act primarily through the central nervous system, this distribution study shows that at the peak of the hypotensive response less than 2% of the injected dose is present in brain and at least equal concentrations of the drug are found in most peripheral tissues. Thus the possibility of peripheral mechanisms contributing to the hypotensive effect cannot be dismissed.