Pro-erectile Effect of Vardenafil: In Vitro Experiments in Rabbits and In Vivo Comparison with Sildenafil in Rats

Giuliano, François; Bernabé, Jacques; Alexandre, L; Niewoehner, U.; Haning, Helmut; Bischoff, Erwin

doi:10.1016/s0302-2838(03)00377-4

Cited by 26 publications

(17 citation statements)

References 9 publications

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“…Opiate antagonists +/− (Leyton and Stewart, 1996;Rodriguez-Manzo and Fernandez-Guasti, 1995;Pfaus and Wilkins, 1995;Sachs et al, 1981;van Furth and van Ree, 1994) Nitric oxide NO agonists + (Benelli et al, 1995;Ferrari et al, 2002;Giuliano et al, 2003) Although NO is a major facilitator of parasympathetically mediated erections, it may inhibit sympathetically mediated seminal emission and ejaculation (Moses and Hull, 1999). Benelli et al, 1995;Bialy et al, 1996;Hull et al, 1994) nitric oxide (NO), in both basal and female-stimulated conditions (reviewed in Dominguez and Hull, 2005;Hull et al, 2006).…”

Section: Ne Antagonists − (Clark and Smith 1990)mentioning

confidence: 99%

Sexual behavior in male rodents

Hull

Domínguez

2007

Hormones and Behavior

392

272

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The hormonal factors and neural circuitry that control copulation are similar across rodent species, although there are differences in specific behavior patterns. Both estradiol (E) and dihydrotestosterone (DHT) contribute to the activation of mating, although E is more important for copulation and DHT for genital reflexes. Hormonal activation of the medial preoptic area (MPOA) is most effective, although implants in the medial amygdala (MeA) can also stimulate mounting in castrates. Chemosensory inputs from the main and accessory olfactory systems are the most important stimuli for mating in rodents, especially in hamsters, although genitosensory input also contributes. Dopamine agonists facilitate sexual behavior, and serotonin (5-HT) is generally inhibitory, though certain 5-HT receptor subtypes facilitate erection or ejaculation. Norepinephrine agonists and opiates have dose-dependent effects, with low doses facilitating and high doses inhibiting behavior.

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Section: Ne Antagonists − (Clark and Smith 1990)mentioning

confidence: 99%

Sexual behavior in male rodents

Hull

Domínguez

2007

Hormones and Behavior

392

272

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“…[7][8][9][10] Some drugs such as inhibitors of PDE 5 or other vasodilators, which can promote the relaxation of corpus cavernosum smooth muscle, can be potentially used to treat ED. [11][12][13][14][15][16][17][18][19] It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. [20][21][22][23][24] Recently, there is an increasing interest in investigating their effective components.…”

Section: Introductionmentioning

confidence: 99%

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

et al. 2009

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It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC 50 1.58 Â 10 À4 mol l À1 ), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration-response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg À1 ). The ICP increased from baseline to 19.1±3.7, 24.8±2.1, 30.2 ± 4.8 and 39.7 ± 6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5 ± 2.8 to 22.9 ± 7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase.

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“…Vardenafil also demonstrated effectiveness in an anesthetized rabbit model with pelvic nerve stimulation 2 and in a rat model, displaying greater efficacy on erectile response than sildenafil at comparable doses. 4 Efficacy in vivo not only depends on the potency and the selectivity of a particular PDE5 inhibitor, but also on its pharmacokinetic (PK) properties. They can be characterized by its absorption, distribution, metabolism, and excretion.…”

Section: Introductionmentioning

confidence: 99%

Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events

Bischoff

2004

Int J Impot Res

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Vardenafil potently inhibits human phosphodiesterase 5 (PDE5) with an IC 50 of 0.7 nM. Enhancement of nitric oxide (NO)-induced erections in rabbits by 0.1 mg/kg vardenafil is limited by its pharmacokinetic properties (T max ¼ 1 h; T 1/2 ¼ 1.2 h), although erectile effects have been observed after 7 h. In humans, vardenafil is rapidly absorbed (T max E40 min) and more slowly metabolized (T 1/2 E4 h), with an absolute bioavailability of 14.5% (vs 40% for sildenafil). Although the consumption of high-fat meals does not affect the drug's relative bioavailability, it retards intestinal absorption. Coadministration of CYP3A4 inhibitors such as ritonavir can affect hepatic metabolism. M1, an active metabolite of vardenafil, is a four-fold-less potent inhibitor of PDE5 than its parent compound, contributing approximately 7% to vardenafil's overall efficacy. The side effects of all selective PDE5 inhibitors commonly include vasodilation, small reductions in blood pressure, headache, and nasal congestion.

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Pro-erectile Effect of Vardenafil: In Vitro Experiments in Rabbits and In Vivo Comparison with Sildenafil in Rats

Cited by 26 publications

References 9 publications

Sexual behavior in male rodents

Sexual behavior in male rodents

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events

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