The pharmacokinetics of yohimbine in man

Berlan

1989

British J Pharmacology

1 The effects of yohimbine (0.5mg kg-i.v.) on both resting and parasympathetic and sympathetic stimulation-induced submaxillary salivary responses were investigated in the anaesthetized dog. 2 Salivary secretion was increased significantly for a period of 45min following an injection of yohimbine. 3 Sectioning of the chorda tympani (but not the cervical sympathetic) nerve abolished the yohimbine-induced increase in resting salivary secretion and potentiated that elicited by electrical stimulation of the chorda tympani nerve. 4 These results show that yohimbine increases submaxillary secretion by inhibition of presynaptic a2-adrenoceptors located on the chorda tympani, which inhibit cholinergic transmission.

Section: Discussionmentioning

confidence: 92%

Effects of yohimbine on submaxillary salivation in dogs

Berlan

1989

British J Pharmacology

“…This observation can be explained by the short half-life of the drug: 0.6 to 1.0 h according to Owen et al (1987) and Guthrie et al (1990) although long-active metabolites were recently described (Le Verge et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants.

Bagheri

Schmitt

Berlan

et al. 1992

Brit J Clinical Pharma

The effect of yohimbine treatment (4 mg three times daily) for 3 weeks on salivary secretion was investigated. In healthy volunteers, acute administration of yohimbine increased salivary volume within 1 h to a similar extent before and at the end of the treatment period. In depressed patients treated with tricyclic antidepressants (and exhibiting a reduced salivary flow), yohimbine also acutely increased salivary volume. In contrast, the alpha 2‐adrenoceptor antagonist failed to modify resting values measured in the morning (i.e. 10 and 14 h after the last administration in healthy volunteers and depressed patients respectively). This result indicates that alpha 2‐adrenoceptor antagonists may have a potential therapeutic use in the treatment of dry mouth caused by tricyclic antidepressant drugs.

“…The data of urinary excretion and partitioning into red blood cells revealed that the rapid plasma clearance of yohimbine may result from the metabolism (a first-pass effect) but not from the renal elimination or sequestration by red blood cells (9). Based on these findings, it is probable that the stimulatory effect of yohimbine on ejaculation in dogs is related to an active metabolite(s) of the compound.…”

Section: Discussionmentioning

confidence: 94%

Long-lasting effects of yohimbine on the ejaculatory function in male dogs

et al. 2005

Previous studies have demonstrated that systemic administration of a low dose of the alpha2-adrenoceptor antagonists stimulates the ejaculatory response of male dogs, when this function is analyzed using the amount of ejaculated semen in response to genital stimulation. The present study was designed to further examine the features of the stimulatory effects of the alpha2-adrenoceptor antagonists on ejaculation, especially the duration of action. Treatment with yohimbine (0.1 mg/ kg, i.p.) to male dogs, at 0.5, 1, 3, or 5 h before the testing, produced a significant stimulatory effects on the ejaculatory response elicited by manual penile stimulation; the amount of ejaculated semen was increased and the onset of ejaculation was shortened following each treatment. However, such effects were not observed in the treatment with yohimbine at 8 and 24 h before the testing, indicating that the ejaculatory stimulation induced by yohimbine lasted for a relative long period. By contrast, the stimulatory effects of RX821002 (0.1 mg/kg, i.p.), a selective alpha2-adrenoceptor antagonist, on ejaculation were observed only for 1 h after administration. To determine the contribution of the alpha2-adrenoceptor blockade for the long-lasting effect of yohimbine, we tested whether yohimbine can prevent the ejaculatory inhibition induced by clonidine, an alpha2-adrenoceptor agonist. The ejaculatory inhibition (a decrease in the amount of ejaculated semen and a delay onset of ejaculation) elicited by clonidine (0.05 mg/kg, i.p.; 1 h before testing) was completely blocked by pretreatment with yohimbine at 1 or 5 h before the testing, whereas the pretreatment with the drug at 24 h before the testing did not affect the clonidine-induced ejaculatory inhibition. These results indicate that yohimbine-induced ejaculatory stimulation is continued for a relative long period (at least 5 h after administration), and this long-lasting effects may be related to the alpha2-adrenoceptor blocking property of the drug.Research has indicated that central alpha2-adrenergic mechanisms may be involved in regulation of male sexual performance. A number of studies have demonstrated that the compounds with central alpha2-adrenoceptor blocking action can facilitate both sexual arousal and copulatory events associated with male sexual behavior (5-7, 10-11). With regard to male sexual function especially ejaculation, however, pharmacological research has been hampered by the lack of a suitable animal model. We have previously established a dog model, which analyzes using the amount of ejaculated semen in response to the genital stimulation as an index for a quantitative assessment of the ejaculatory capacity (15). Using this model, we reported for the first