Yohimbine enhances the effect of sildenafil on erectile process in rats

Abstract

Combining the centrally acting drug yohimbine with the peripheral conditioner sildenafil might be an approach to erectile dysfunction cases in which sildenafil alone failed. This work aimed to investigate the effect of yohimbine on sildenafil-induced facilitation of erectile process. Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded. Intracavernosal pressure/systemic arterial pressure (ICP/SAP) was calculated, 1 and 5 min after intravenous administration of sildenafil, yohimbine or a combination of both. Changes in sexual arousal and copulatory performance indices were compared before and after these injections using behavioral mating experiments. It was shown that systemic administration of sildenafil produced a significant increase in ICP/SAP than control at doses X10 lmol kg À1. Yohimbine alone failed to potentiate erectile responses but yohimbine (1 lmol kg À1) significantly potentiated the effect of sildenafil 1-10 lmol kg À1 and 1 mmol kg À1, 1 and 5 min after injection. Potentiation of ICP/SAP induced by their combination was greater than the sum of the effects of the corresponding doses of either drug at the same time interval. A nonsignificant additional decrease in SAP than sildenafilinduced was observed if administered with yohimbine. Addition of sildenafil to yohimbine significantly enhanced the effect of the latter on intromission frequency, intercopulatory interval and the number of ejaculations per session. It is concluded that yohimbine may enhance and prolong the effect of sildenafil on erectile process without additional hypotension. Sildenafil may enhance the central effects of yohimbine on erection; it amplifies the effect of yohimbine on male copulatory performance but not on sexual motivation. The potential beneficial effect of the combination was found to be more pronounced on the central component than on the peripheral component of the erectile process.

Effects of Cnidium monnieri (L.) Cuss. fruit extract on sexual behaviors in male rats

“…Some scientific evidence proves the role of central dopaminergic system in regulating sexual behavior, including sexual desire in humans and animals. Similar results were obtained from other authors' research including [8][9][10][11] etc. To explain this effect of sildenafil, scientists have theorized the effect of sildenafil on the central nervous system, specifically on the central dopaminergic system [12,13].…”

“…This result is perfectly consistent with the mechanism of action of sildenafil PDEV inhibition, which increases the amount of cGMP that causes vasodilatation, increases intracavernosum pressure, increases erectile function [17,18]. Increased intromission, enhanced sexual intercourse and improved erectile function of sildenafil were also reported in many studies using sildenafil as a positive control [8][9][10][11].…”

BPH/LUTS and ED: Common Pharmacological Pathways for a Common Treatment

“…Furthermore, yohimbine may enhance and prolong the effect of sildenafil on erectile process without additional hypotension. On the other hand, sildenafil may enhance the central effects of yohimbine on erection without amplifying the effect on sexual motivation [24]. There are some other evidences that combination of PDE5‐Is with α‐blockers, such as alfuzosin 10 mg plus sildenafil 25 mg in a pilot study, improves significantly both LUTS and ED [25].…”

Yohimbine relaxes the human corpus cavernosum through a non-adrenergic mechanism involving the activation of K+ATP-dependent channels

“…12 The medicine commonly used for erectile dysfunction, the sildenafil, has its central effect improved when associated to yohimbine. 13 Unlike most published studies, using compromised corpus cavernosum tissues donated by penile prosthesis patients, 4,14 in this study we used samples retrieved from cadaver donors during the removal of organs for transplantation. All donors (n ¼ 12) had died of craniocerebral trauma and, according to relatives, none had suffered from erectile dysfunction.…”