Summary
The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg · kg−1.
Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and IS min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (Vss) was 741, (range 26 to 1271). Only 0.5 to 1 % of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 1171. h−1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1 % of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of theα 2-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man.
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References
Steinegger E, Hänsel R (1988) Lehrbuch der Pharmakognosie und Phytopharmazie. Springer, Berlin, pp 542–546
Goldberg MR, Robertson D (1983) Yohimbine: A pharmacological probe for study of theα 2-adrenoceptor. Pharmacol Rev 35:143–180
Holmberg G, Gershon S, Beck LH (1962) Yohimbine as an autonomic test drug. Nature 193:1313–1314
Charney DS, Heninger GR, Sternberg DE (1982) Assessment ofα 2-adrenergic autoreceptor function in humans: Effects of oral yohimbine. Life Sci 30:2033–2041
Henaur SA, Gillespie HK, Hollister LE (1984) Yohimbine and the model anxiety state. J Clin Psychiatry 45:512–515
Sachs GS, Pollack MH, Brotman AW, Farhadi AM, Gelenberg AJ (1986) Enhancement of ECT benefit by yohimbine. J Clin Psychiatry 47:508–510
Onrot J, Goldberg MR, Biaggioni I, Wiley RG, Hollister AS, Robertson D (1987) Oral yohimbine in human autonomic failure. Neurology 37:215–220
Lecrubier Y, Puech AJ, Des Laurets A (1981) Favourable effects of yohimbine on clomipramine-induced orthostatic hypotension: a double-blind study. Br J Clin Pharmacol 12:90–94
Lacomblez L, Bensimon G, Isnard F, Diquet B, Lecrubier Y, Puech AJ (1989) Effect of yohimbine on blood pressure in patients with depression and ortostatic hypotension induced by clomipramine. Clin Pharmacol Ther 45:241–251
Morales A, Surridge DHC, Marshall PG, Fenemore J (1982) Nonhormonal pharmacological treatment of organic impotence. J Urol 128:45–47
Morales A, Condra M, Owen JA, Surridge DHC, Fenemore J, Harris C (1987) Is yohimbine effective in the treatment of organic impotence: Results of a controlled trial. J Urol 137:1168–1172
Galitzky J, Taouis M, Berlan M, Rivière D, Garrigues M, Lafontan M (1988)α 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers. Eur J Clin Invest 18:587–594
Holmberg G, Gershon S (1961) Autonomic and psychic effects of yohimbine hydrochloride. Psychopharmacol 2:93–106
Diquet B, Lacomblez L, Doare L, Berlin I, Bergougnan L, Simon P. Etude pharmacocinatique de la yohimbine chez l'homme (1985) J Pharmacol [Paris] 16:540
Owen JA, Nakatsu SL, Condra M, Surridge DH, Fenemore J, Morales A (1985) Sub-nanogram analysis of yohimbine and related compounds by high-performance liquid chromography. J Chromatogr 342:333–340
Owen JA, Nakatsu SL, Fenemore J, Condra M, Surridge DHC, Morales A (1987) The pharmacokinetics of yohimbine in man. Eur J Clin Pharmacol 32:577–582
Hjemdahl P, Daleskog M, Kahan T (1979) Determination of plasma eatecholamines by high performance liquid chromatography with electrochemcal detection; comparison with a radioenzymatic method. Life Sci 25:131–138
Persson B, Hedner T, Berglund G (1983) Ketanserin i essential hypertension: Effects during rest and exercise. Eur J Pharmacol 25:307–312
Edvinsson L, Ekman R, Hedner P, Valdemarsson S (1990) Congestive heart failure: involvment of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibers. Eur J Clin Invest 20:85–89
Sheiner L, Beal SL (1985) Pharmacokinetic parametric estimates from several least squares procedures. Superiority of extended least squares. J Pharmacokinet Biopharm 13:185–201
Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Deckker, New York, pp 33–40
Aronson JK, Dengler HJ, Dettli L, Follath F (1988) Standardization of symbols in clinical pharmacology. Eur J Clin Pharmacol 35:1–7
Rasmussen SA, Goodman WK, Woods SW, Heninger GR, Charney DS (1987) Effects of yohimbine in obsessive compulsive disorder. Psychopharmacol 93:308–313
Charney DS, Heninger GR, Sternberg DE (1984) Noradrenergic function in panic anxiety: Effects of yohimbine in healthy subjects and patients with agorafobia and panic disorder. Arch Gen Psychiatry 41:751–763
Charney DS, Redmond DE Jr (1983) Neurobiological mechanisms in human anxiety: Evidence for noradrenergic hyperactivity. Neuropharmacology 22:1531–1536
Hubbard JW, Pfister SL, Beidinger AM, Herzig TC, Keeton TK (1988) The pharmacokinetic properties of yohimbine in the conscious rat. Naunyn-Schmiedeberg's Arch Pharmacol 337:583–587
Altman PL, Dittmer DS (1971) Respiration and circulation. American Societies for Experimental Biology, Bethesda, MD, p 428
Dahlöf C, Dahlöf P, Lundberg JM (1986)α 2-adrenoceptor-mediated inhibition of nerve stimulation-evoked release of neuropeptide Y(NPY)-like immunoreactivity in the pithed guinea-pig. Eur J Pharmacol 131:279–283
Dahlöf P, Tarizzo VI, Lundberg JM, Dahlöf C (1991)α andβ-adrenoceptor mediated effects of nerve stimulation evoked release of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea-pig. J Anton Nerv Syst 35:199–210
Eckberg DL, Andersson OK, Hedner T, Lundberg JM, Rea RF, Walin G (1988) baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans. Acta Physiol Scand 133:221–231
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Hedner, T., Edgar, B., Edvinsson, L. et al. Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers. Eur J Clin Pharmacol 43, 651–656 (1992). https://doi.org/10.1007/BF02284967
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DOI: https://doi.org/10.1007/BF02284967