The pharmacokinetic properties of yohimbine in the conscious rat. Naunyn Schmiedebergs Arch Pharmacol 1988 May;337(5):583-7
Date
05/01/1988Pubmed ID
3412496DOI
10.1007/BF00182736Scopus ID
2-s2.0-0023887892 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
We used high performance liquid chromatography with fluorescence detection to measure the concentration of yohimbine in serum and brain of conscious Sprague-Dawley rats at various times after the i.v. injection of 1 mg/kg of yohimbine. The serum concentration-time profile of yohimbine was biphasic with a rapid distribution phase (t1/2 alpha = 0.048 h) followed by a very slow elimination phase t1/2 beta = 16.3 h). The clearance of yohimbine was 11 ml/h.kg-1, and the volume of distribution was 259 ml/kg. Increasing doses (0.3, 1 and 3 mg/kg, i.v.) of yohimbine produced non-linear increases in serum yohimbine concentration. Yohimbine entered the brain rapidly (5,000 ng/g at 5 min after 1 mg/kg, i.v.) and disappeared from brain with a t1/2 beta of 7.7 h. In contrast to serum yohimbine concentration, increasing doses of yohimbine (0.3, 1 and 3 mg/kg) produced linear increases in brain yohimbine concentration, a phenomenon which is consistent with concentration-dependent binding of yohimbine to plasma proteins. The rapid entry of yohimbine into the brain, the slow rate of elimination of yohimbine from serum and brain and the linear relationship of brain yohimbine concentration as a function of dose should be taken into consideration whenever yohimbine is to be used as a probe of alpha 2-adrenoceptor function in vivo.
Author List
Hubbard JW, Pfister SL, Biediger AM, Herzig TC, Keeton TKAuthor
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBrain
Chromatography, High Pressure Liquid
Injections, Intravenous
Male
Rats
Rats, Inbred Strains
Spectrometry, Fluorescence
Yohimbine
