• Korean Journal of Clinical Pharmacy
• /
• v.25 no.1
• /
• pp.50-55
• /
• 2015

Background: Phosphodiesterase Type 5 Inhibitors (PDE5Is), which are prescription drug in South Korea, have been concerned about misuse, overuse and illegal provision of the drugs. This study was performed to investigate utilization and safety of illegal Phosphodiesterase Type 5 Inhibitors (PDE5Is), and related factors among South Korean men. Methods: A questionnaire survey was conducted from May to July in 2013 among 1,500 nationally representative general males using computer-assisted telephone interview (CATI). The questionnaire included the characteristics of population, the characteristics of PDE5Is use, the experience with the use of illegally obtained PDE5Is, and adverse events after PDE5Is use. Results: Among study population, the 1,015 (67.7%) men answered that they have used the illegally obtained PDE5Is. Younger age, single, lower frequency of PDE5Is use in a lifetime was associated with an increased use of illegally obtained PDE5Is. The men experienced adverse events after PDE5Is use is 528 (35.2%). The most common adverse event was mild to moderate hot flashes. Conclusion: We need to enhance awareness about the risk of illegally obtained PDE5Is use, especially in younger men and single. Proactive educations and public relations on safe use of PDE5Is for proper patients are needed.

• Korean Journal of Pharmacognosy
• /
• v.43 no.2
• /
• pp.184-191
• /
• 2012

The aim of this study was to explore the potent phosphodiesterase type 5 (PDE %) inhibitor from various herbal medicines for erectile dysfunctions. In this study, 61 herbal medicines, which were extracted with ethanol, have been investigated with PDE 5 assay using enzyme inhibitory activity on 22 species of herbal medicines. Of these, 5 species of herbal medicines, Cnidium monieri, Cuscuta chinensis, Epimedium koreanum, Morinda officinalis, and Tribulus terrestris were exhibited stronger inhibitory effect against phosphodiesterase 5 (PDE 5) among 61 species; Cnidium monieri ($IC_{50}=33.7{\mu}g/ml$), Cuscuta chinensis ($IC_{50}=65.7{\mu}g/ml$), Epimedium koreanum ($IC_{50}=90.3{\mu}g/ml$), Morinda officinalis ($IC_{50}=48.7{\mu}g/ml$) and Tribulus terrestris ($IC_{50}=32.5{\mu}g/ml$).

• The Korean Journal of Zoology
• /
• v.29 no.2
• /
• pp.79-85
• /
• 1986

The purpose of the present experiment is to make certain the exsistence of cAMP phosphodiesterase (PDE) in mouse oocytes and confirm its possible role on meiotic resumption. The results showed two types of cAMP in the oocytes with different Michaelis constants (Km) with specific maximum (Vmax); The Km and Vmax of one of two types of PDE were estimated at $0.14 \\pm 0.01 \\muM$ and $0.42 \\pm 0.07$ fmol cAMP hydrolyzed/oocyte/minute, and the other at $14.5 \\pm 2.0 \\muM$ and $2.2 \\pm 0.5$ fmol cAMP hydrolyzed/oocyte/minute. cAMP hydrolysis by PDE was reversibly inhibited in vitro by presence of theophylline or isobutyl-methyl-xanthine (IBMX), which is well known as an inhibitor of oocyte maturation. Consequently, it can be assumed that maturation of oocyte is affected by the high level of intracellular cAMP, and its level is well maintained by presence of PDE inhibitor, such as theophylline and IBMX.

• Journal of Life Science
• /
• v.22 no.2
• /
• pp.281-284
• /
• 2012

This study demonstrated that upregulation of gene expression of endoplasmic reticulum (ER) stress chaperones (Bip, ERp29, calnexin, and PDI), ER stress sensors (PERK, ATF6, and Ire1), and cAMP phosphodiesterase 7A1 (cAMP PDE7A1) was induced by ER stresses in FRTL5 cells. While removing A23187 from the culture medium restored upregulation of cAMP PDE7A1 gene expression, removal of thapsigargin did not recover its expression. In addition, cAMP PDE7A1 gene expression was strongly inhibited by treatment with A23187 combined with thyroid stimulating hormone (TSH). The results are the first to show that ER stress induces cAMP PDE7A1 gene expression.

• Clinical and Experimental Reproductive Medicine
• /
• v.43 no.1
• /
• pp.26-30
• /
• 2016

Objective: We aimed to investigate the prevalence of erectile dysfunction (ED) and the usage of phosphodiesterase type 5 (PDE5) inhibitors for ED treatment in infertile couples. Methods: A total of 260 male partners in couples reporting infertility lasting at least 1 year were included in this study. In addition to an evaluation of infertility, all participants completed the International Index of Erectile Function (IIEF)-5 questionnaire to evaluate their sexual function. The participants were asked about their use of PDE5 inhibitors while trying to conceive during their partner's ovulatory period and about their concerns regarding the risks of PDE5 inhibitor use to any eventual pregnancy and/or the fetus. Results: Based on the IIEF-5 questionnaire, 41.5% of the participants (108/260) were classified as having mild ED (an IIEF-5 score of 17-21), while 10.4% of the participants (27/260) had greater than mild ED (an IIEF-5 score of 16 or less). The majority (74.2%, 193/260) of male partners of infertile couples had a negative perception of the safety of using a PDE5 inhibitor while trying to conceive. Only 11.1% of men (15/135) with ED in infertile couples had used a PDE5 inhibitor when attempting conception. Conclusion: ED was found to be common in the male partners of infertile couples, but the use of PDE5 inhibitors among these men was found to be very low. The majority of male partners were concerned about the risks of using PDE5 inhibitors when attempting to conceive. Appropriate counseling about this topic and treatment when necessary would likely be beneficial to infertile couples in which the male partner has ED.

• Childhood Kidney Diseases
• /
• v.6 no.1
• /
• pp.85-91
• /
• 2002

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${\beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${\beta}1$. Materials and Methods : Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-${\beta}1$ in renal tissue- conditioned media was measured by ELISA. Results : Masson- trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson- trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-${\beta}1$ concentration among the groups. Conclusion: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${\beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)

• Archives of Pharmacal Research
• /
• v.25 no.6
• /
• pp.873-878
• /
• 2002

OA-8159, a new Phosphodiesterase (PDE) 5 inhibitor, has exhibited potent erectogenic potential in a penile erection test in rats and anesthetized dogs. In this study, we investigated the mechanism of its erectogenic activity by measuring the activity of OA-8159 against a various PDE isozymes and assessing cGMP and cAMP formation in a rabbit corpus cavernosum in vitro. DA-8159 inhibited the PDE 5 activity in rabbit and human platelets, which the $IC_{50}$ was 5.84$\pm$1.70 nM and 8.25$\pm$2.90 nM, respectively. The $IC_{50}$ of DA-8159 on PDE 1, PDE2, PDE 3 and PDE 6 were 870$\pm$57.4 nM, $101\pm$5 $\mu$M, 52.0$\pm$3.53 $\mu$M and 53.3$\pm$2.47 nM, respectively. This suggests that DA-8159 is a potent, highly selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5~100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. DA-8159 increased the apparent 4K_{m}$ value for cGMP hydrolysis but had no effect on the apparent $V_{max}$, indicating a competitive mode of inhibition. DA-8159 increased the cGMP concentrations in the rabbit corpus cavernosum dose dependently. In the presence of sodium nitroprusside (SNP), DA-8159 significantly sti\mulated the accu\mulation of cGMP when compared to the control level. This indicated that the enhancement of a penile erection by DA-8159 involved the relaxation of the cavernosal smooth \muscle by NO-sti\mulated cGMP accu\mulation. In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth \muscle by the NO-sti\mulated cGMP accu\mulation.

• Korean Journal of Clinical Pharmacy
• /
• v.30 no.1
• /
• pp.59-64
• /
• 2020

The emergence of phosphodiesterase (PDE) 5 inhibitors gave rise to the solution for erectile dysfunction, starting with the development of sildenafil. Although their efficacy in treating erectile dysfunction has been shown, the side effects of PDE5 inhibitors, especially sildenafil, must be taken into consideration. A 64-year-old man received 100 mg of sildenafil and experienced blue vision in both eyes; however, after a day or so, his symptoms improved. The symptoms disappeared when he stopped administering sildenafil, but reappeared when the medication was re-administered. Therefore, he discontinued sildenafil treatment and was prescribed udenafil instead. After that, visual adverse events no longer occurred. Causality assessment showed that in this case, sildenafil-induced cyanopsia was "certain" under the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria and Korean causality assessment algorithm (Ver.2), and was "probable" according to the Naranjo scale. In addition, sildenafil also led to abnormal visual reactions in other cases. Sildenafil can also inhibit PDE6, which is present in retinal cells, unlike other PDE5 inhibitors. Thus, visual adverse reactions, such as blue vision, are the unique results of sildenafil, and other PDE5 inhibitors may be used to prevent them.

• Mass Spectrometry Letters
• /
• v.3 no.2
• /
• pp.50-53
• /
• 2012

After success of sildenafil for the treatment of erectile dysfunction, a large number of its analogues have been approved from FDA. Recently, the illegal dietary supplements which include sildenafil, vardenafil, tadalafil, or analogues of these drugs as ingredient have been widely distributed. Therefore, the determination of the residue of synthetic phosphodiesterase- 5 (PDE-5) inhibitors in dietary supplements is highly required due to indiscriminate and unintentional overdose caused nausea, chest pains, fainting and irregular heartbeat. In this paper, we report a rapid and sensitive analytical method for the simultaneous determination of nine phosphodiesterase-5 inhibitors by liquid chromatography-high resolution mass spectrometry. The present method was found to be accurate and reproducible with 40 ${\mu}g$/g of the limit of quantification for the nine PDE-5 inhibitors. The developed method can be successfully applied to the analysis of the seven illegal dietary supplements.

• Korean Journal of Veterinary Research
• /
• v.40 no.3
• /
• pp.479-487
• /
• 2000

Several recent studies demonstrate that receptor-mediated cAMP (adenosine 3',5'-monophosphate) production evokes marked change in magnesium ($Mg^{2+}$) homeostasis. The effects of dimaprit or/and phosphodiesterase (PDE) inhibitors on the $Mg^{2+}$ release from perfused guinea pig heart and collagenase-dispersed myocytes was studied to clarify an association of $H_2-histaminergic$ receptor-mediated $Mg^{2+}$ regulation with intracellular cAMP-degradation system. $Mg^{2+}$ efflux was stimulated in perfused hearts and myocytes by IBMX (3-isobutyl-1-methylxanthine), a calmodulin-sensitive PDE inhibitor, but not by RO 20-1724(4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) or papaverine, cAMP-specific PDE inhibitors. $Mg^{2+}$ efflux was also be induced by dimaprit, a H-2-agonist. $Mg^{2+}$ effluxes induced by dimaprit were augmented by the presence of the PDE inhibitors. The augmentation of dimaprit-induced $Mg^{2+}$ effluxes by the PDE inhibitors were inhibited by ranitidine, a $H_2-antagonist$, and imipramine, a $Na^{+}-Mg^{2+}$ exchange inhibitor, in perfused hearts and myocytes and were also inhibited by amiloride in perfused hearts. These results suggest that the $H_2$-stimulated $Mg^{2+}$ effluxes from guinea pig heart can be regulated by the cytosolic nonspecific-dependent PDE systems and that it is induced by the $Na^{+}-Mg^{2+}$ exchanger stimulation.