Effect of phosphodiesterase inhibitors in the bladder

Many aging men will experience lower urinary tract symptoms(LUTS).Phosphodiesterase type 5(PDE5)inhibitors have shown promise in treating LUTS in these patients.PDE5 inhibitors mediate their effects through several pathways including cAMP,NO/cGMP,Kchannel modulated pathways,and the L-cysteine/H2S pathway.PDE5 inhibitors exert their effect in muscle cells,nerve fibers,and interstitial cells(ICs).The use of PDE5 inhibitors led to improvement in LUTS.This included urodynamic parameters.PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

Effects of phosphodiesterase 5 inhibitors on sperm parameters and fertilizing capacity

The aim of this review study is to elucidate the effects that phosphodiesterase 5 （PDE5） inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase （AC） system and the cGMP/guanylate cyclase （GC） system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide （NO） leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil＇s actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology （ART） programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

The use of antimuscarinics,phosphodiesterase type Ⅴ inhibitors and phytotherapy for lower urinary tract symptoms in men

Besides the mainstay of α-blockers and 5α-reductase inhibitors,other forms of medical therapy complete the armamentarium in the treatment of lower urinary tract symptoms(LUTS)in men.These treatments can target specific symptoms as well as associated symptoms that would affect the quality of life of the patients.Many patients are bothered by storage symptoms,more so than the voiding symptoms.Antimuscarinics are efficacious and safe,provided the patients do not have high post void residual urine.Many patients with LUTS also have erectile dysfunction,and phosphodiesterase type Ⅴ inhibitors are effective in relieving both LUTS as well as erectile dysfunction for such patients.Phytotherapy provides a popular and safe treatment for LUTS,however,the efficacy of the treatment has not been proven in well conducted prospective randomized controlled studies.

Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor in patients with multiple risk factors

1 Introduction With the 1998 introduction of sildenafil (Viagra), the first available oral phosphodiesterase inhibitor, there

Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor with concurrent sex therapy

1 Introduction Erectile dysfunction (ED) is a condition that affects perhaps 25 to 30 million men in the U.S.A. constituting

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats

Aim： To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 （PDE5） inhibitor, on penile erection in obese rats. Methods： The rats were fed a high-energy diet for 12 weeks and divided into three groups： an obesity-resistant （OR） control group, an obesity-prone （OP） control group, and an OP-DA-8159 treatment （DA-8159） group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results： In the OP control group, the maximum intracavernous pressure （ICP） and ICP/blood pressure （ICP/BP） ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve （AUC） of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion： These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction （ED） can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Prevalence and medical management of erectile ：lysfunction in Asia

Erectile dysfunction （ED） is an important worldwide health issue that has a significant negative impact on the quality of life and life satisfaction of both the affected individual and his partner. Here we review the prevalence of ED in Asia, associated factors that may influence sexual attitudes and sexual behaviours, and randomized clinical trials （RCTs） of phosphodiesterase-5 （PDE-5） inhibitors to evaluate the clinical efficacy and safety of PDE-5 inhibitors in Asian men. We searched for English-language articles in MEDLINE and PubMed from January 2000 to September 2010. Our results showed that the overall reported prevalence rate of ED in Asia ranged widely, from 2% to 88%. This finding indicates that ED is a common and major health problem in this region. However, sociocultural and economic factors in Asia prevent people from seeking and obtaining appropriate medical care. We found reports on five kinds of PDE-5 inhibitors for the management of ED.＇ sildenafil, vardenafil, tadalafil, udenafil and mirodenafih The results of RCTs showed that these five PDE-5 inhibitors are more effective than placebo in improving erectile function in Asian men with ED and that these drugs have similar efficacy and safety profiles.

New oral agents for erectile dysfunction: what is changing in our practice?

Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and isassociated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, aswell as numerous age - related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A ratio-nal step - wise approach which includes comprehensive medical and sexual history, a focused physical examination andessential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnos-tic work - up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penilepharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate onlyin the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable riskfactors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with newmolecules (phosphodiesterase inhibitors or apomorphine) is the first - line treatment for the majority of patients becauseof potential benefits and lack of invasiveness. (Asian J Androl 2001 Sep; 3: 175-179 )

Efficacy and safety of tadalafil taken as needed for the treatment of erectile dysfunction in Asian men： results of an integrated analysis

We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population （with varying patient demographics, disease severity, and comorbid medical conditions） of Asian men with erectile dysfunction （ED）. An integrated analysis of five double-blind, placebo-controlled trials （N = 1 046） was performed. Patients were randomly assigned to receive 10 mg tadalafil （N = 185）, 20 mg tadalafil （N = 510）, or placebo （N = 351）. Efficacy assessments included the International Index of Erectile Function （IIEF）, Sexual Encounter Profile （SEP） diary and Global Assessment Question （GAQ）. Patients receiving 10 mg or 20 mg tadalafil showed significant improvement from baseline-to-end point on the Erectile Function domain of the International Index of Erectile Function （IIEF-EF） domain score in all clinical sub-populations analyzed, compared with patients receiving placebo （P 〈 0.001）. The 10-mg and 20-mg tadalafil groups showed a mean success rate of 64.1% and 70.5% for sexual intercourse attempts （SEP3, successful intercourse）, respectively, compared with 33.4% in the placebo group （P 〈 0.001）, and 85.5% and 85.4% reported improved erections at end point GAQ, respectively, versus 43.5% in the placebo group （P 〈 0.001）. Tadalafil was well tolerated across all groups studied. Headache and back pain were the most frequently reported adverse events. Overall, tadalafil was effective and well tolerated across a diverse clinical spectrum of Asian men with ED.

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction

Aim： To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 （PDE-5） inhibitor, in men of Asian ethnicity with erectile dysfunction （ED）. Methods： In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil （10 mg） or placebo （4：1 ratio） for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain （IIEF-EF）, and Sexual Encounter Profile （SEP） questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question （GAQ） on erection improvement. Results： Least-squares mean baseline IIEF-EF domain scores （vardenafil 14.6, placebo 13.4） were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo （22.4 vs. 14.3; P 〈 0.001）. Vardenafil was associated with significant improvements from baseline in least squares （LS） mean success rates for SEP-2 （vardenafil 82.2 vs. placebo 43.6; P 〈 0.001） and SEP-3 （vardenafil 66.1 vs. placebo 24.0; P 〈 0.001）. Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. Conclusion： Vardenafil （10 mg） is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.

Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells

In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1 × 10^-5 mol I^-1 norepinephrine, GBE （0.01-1 mg ml^-1） and mirodenafil （0.01-100 nmol I^-1） were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavemosum was relaxed in response to GBE in a dose-dependent manner （from 0.64%±8.35% at 0.01 mg ml^-1 to 52.28%±11.42% at 1 mg ml^-1）. After pre-treatment with 0.03 mg ml^-1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations, After tetraethylammonium （TEA） （1 mmol I^-1） administration, the increased effects were inhibited （P〈0.01）. Extracellular administration of GBE increased the whole-cell K^＋ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by I mmol 1-1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K＋ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.

Sexual dysfunctions and their treatment in liver diseases

Sexual dysfunction(SD)is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis.The etiology of SD is multifactorial and therefore treatment strategies are complex,especially in females.Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females,no single drug is available for SD,therefore multimodal treatment is required depending upon the cause.The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases.Improved quality of life is helpful in improving SD and vice versa is also true.Therefore,patients suffering from liver diseases should come forward and ask for treatment for SD,and physicians should actively enquire about SD while history taking and evaluating these patients.SD results in deterioration of quality of life,and both are modifiable and treatable aspects of liver diseases,which are never addressed actively,due to social taboos and fears of SD treatment in the presence of liver diseases.The diagnosis of SD does not require costly investigations,as the diagnosis can be established based on validated questionnaires available for both genders,therefore detailed targeted history taking using questionnaires is essential.Data are emerging in this area but is still at an early stage.More studies should be dedicated to SD in liver diseases.

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction:a randomized double-blind,parallel,placebo-controlled clinical study

Aim： To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction （ED）, Methods： This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed （maximum once daily）. Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Results： Tadalafil significantly improved erectile function as compared to the placebo （P 〈 0.001）. At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts （Sexual Encounter Profile question 3： 70.9% compared to 33.5% in the placebo） and a greater proportion of improved erections （Global Assessment Question： 86.2% compared to 30.1%）. Most （≥3%） treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Conclusion： Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

Recent insights into androgen action on the anatomical and physiological substrate of penile erection

Erectile response is centrally and peripherally regulated by androgens. The original insights into the mechanisms of action of androgens were that androgens particularly exert effects on libido and that erections in response to erotic stimuli were relatively androgen-independent. It was shown that sexual functions in men required androgen levels at the low end of reference values of testosterone. So it seemed that testosterone was not useful treatment for men with erectile difficulties, particularly following the advent of the phosphodiesterase type 5 （PDE5） inhibitors. However, approximately 50% of those treated with PDE5 inhibitors discontinue their treatment. A number of recent developments shed new light on testosterone treatment of erectile dysfunction （ED） in aging men. （1） A recent insight is that, in contrast to younger men, elderly men might require higher levels of testosterone for normal sexual functioning. （2） Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men, and that testosterone improves the therapeutical response to PDE5 inhibitors considerably. （3） There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, reversible upon androgen replacement. The synthesis of PDE5 is upregulated by androgens, and the arterial inflow into the penis is improved by giving androgen. The above invites a re-examination of the merits of giving testosterone to aging men with ED. The beneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment. （Asian J Androl 2006 Jan; 8： 3-9）

Influence of erectile dysfunction course on its progress and efficacy of treatment with phosphodiesterase type 5 inhibitors

Background Erectile dysfunction （ED） is a common impairment among older men, and the prevalence rates increase sharply after age of 60 years. Most studies have focused on the prevalence rate or dangerouse factors. The aim of this study was to investigate the basic epidemiologic data about ED patients with different ED courses. The purpose of this researth was to understand the therapeutic effect of phosphodiesterase type 5 inhibitor （PDE5-1） and see how and why the ED course impact the progress of ED and the therapeutic effect of PDE5-1 treatment. Methods From June 2008 to June 2009, 4252 questionnaires （Quality of Erection Questionnaire, QEQ） were gathered from 46 centers by urology or andrology doctors all around China. Patients with ED （age 〉 20 years） filled in first half of the questionnaires when they came for the first time, and then completed the second half 4 weeks after PDE5-1 therapy. Results ED courses of most patients were less than 5 years （〈5 years, 74.0%; 5-10 years 20.8%; 〉10 years, 5.2%）. As ED course increasing, the incidence of the risk factors of ED, such as smoking, drinking, hypertension, diabetes, heart disease and hyperlipidemia also increase （P 〈0.01）. PDES-I was effective in improving the quality of sexual activities （P 〈0.01）. Administration of PDE5-1 improves satisfaction, enjoyment and frequency of sexual activities. The longer the ED course, the worse the therapeutic effect （〈5 years, 96.1%; 5-10 years, 94.9%; 〉10 years, 89.0%） （P 〈0.01）. Conclusions The ED course greatly affected the therapeutic effect of PDE5-1, the patients with ED should consult doctor at early stage of the disease. Admistration of PDE5-1 effectively improves the penile erection and the quality of sexual life of the patients hence should be considered as first-line medicine in the treatment of ED.

Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors： an update

Phosphodiesterase isoenzymes 5 inhibitors （PDE5-1s） are the first-line therapy for erectile dysfunction （ED）. The constant discoveries of nitric oxide （NO）/cyclic guanosine monophosphate （cGMP） cell-signaling pathway for smooth muscle （SM） control in other urogenital tracts （UGTs） make PDE5-1s promising pharmacologic agents against other benign urological diseases. This article reviews the literature and contains some previously unpublished data about characterizations and activities of PDE5 and its inhibitors in treating urological disorders. Scientific discoveries have improved our understanding of cell-signaling pathway in NO/cGMP-mediated SM relaxation in UGTs. Moreover, the clinical applications of PDE5-1s have been widely recognized. On-demand PDE5-1s are efficacious for most cases of ED, while daily-dosing and combination with testosterone are recommended for refractory cases. Soluble guanylate cyclase （sGC） stimulators also have promising role in the management of severe ED conditions. PDE5-1s are also the first rehabilitation strategy for postoperation or postradiotherapy ED for prostate cancer patients. PDE5-1s, especially combined with （z-adrenoceptor antagonists, are very effective for benign prostatic hyperplasia （BPH） except on maximum urinary flow rate （Qmax） with tadalafil recently proved for BPH with/without ED. Furthermore, PDE5-1s are currently under various phases of clinical or preclinical researches with promising potential for other urinary and genital illnesses, such as priapism, premature ejaculation, urinary tract calculi, overactive bladder, Peyronie＇s disease, and female sexual dysfunction. Inhibition of PDE5 is expected to be an effective strategy in treating benign urological diseases. However, further clinical studies and basic researches investigating mechanisms of PDE5-1s in disorders of UGTs are required.

Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH

The aim of this systematic review is to determine the comparative effectiveness and safety of phosphodiesterase 5 inhibitors （PDE5-1s） and （x-blockers used alone or combined for the treatment of lower urinary tract symptoms （LUTS） due to benign prostatic hyperplasia （BPH）. An electronic search of PubMed, Cochrane Library and Embase up to January 2014 was performed to identify randomized controlled trials comparing the efficacy and safety of PDE5-Is and （x-blockers for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual urine, quality of life and Erectile Function （IIEF） score as outcomes. Data were analyzed by fixed or random effect models using Cochrane Collaboration review manager software. A total of 12 studies were included, Our novel data demonstrated that there was a trend that （x-blockers were more efficacious than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. （x-blockers were significantly more effective than PDE5-Is on reduction of postvoided residual urine with a mean difference of 3.67 （95% CI 1.56 to 5.77, P = 0.0006） and PDE5-Is showed greater effect than （x-blockers on increasing IIEF score with a mean difference of 9.82 （95% CI 3.80 to 15.85, P = 0.001）. In conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this kind of disorder except less reduction of PVR than ABs, In addition, both combined- or mono-therapy were safe.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors （PDE5-1s） for erectile dysfunction （ED） varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-1s with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration＇s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-1s were grouped together, Caucasian ethnicity was associated with 15.636% （95% confidence interval [CI]： 0.858% to 32.579%） increase in risk ratio （RR） for Global Assessment Questionnaire question-1 （GAQ-1）, and 1.473 （95% CI： 0.406 to 2.338） score increase in mean difference （MD） for posttreatment International Index of Erectile Function-Erectile Function domain score （IIEF-EF）, compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% （95% CI： -9.120% to -2.017%） reduction in RR for GAQ-1, and -0.229 （95% CI： -0.425 to -0.042） score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-1s are more effective in Caucasians than Asians, and in patients with more severe ED.

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P