• 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 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.

• 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.

• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.3
• /
• pp.369-376
• /
• 1998

This report shows that hydroxyl radical, generated by a Fenton reaction involving adenosine $5'-diphosphate/Fe^{2+}$ complex ($5-15\;{\mu}M$) and $H_2O_2$ ($2\;{\mu}M$), induced differentiation of HL-60 cells in a dose- and time-dependent manner. This is evidenced by the increases in 12-O-tetradecanoylphorbol 13-acetate- and fMLP-stimulated superoxide production capability. The cells exposed to hydroxyl radical for defined periods (24∼96 hr) continued to differentiate even after the hydroxyl radical generating system had been removed. The differentiated cells displayed fMLP-stimulated calcium mobilization and increased expression of myeloid-specific antigen CD11b and CD14. The extent of the differentiation was markedly reduced by desferrioxamine ($100\;{\mu}M$), dimethylthiourea (5 mM), N,N'-diphenyl-1,4-phenylenediamine ($2\;{\mu}M$), and N-acetyl-L-cysteine (5 mM). The induction of differentiation by hydroxyl radical was enhanced by 3-isobutyl-1-methylxanthine ($200\;{\mu}M$) and Ro-20-1724 ($8\;{\mu}M$), and inhibited by dipyridamole (2 ${\mu}M$). These results suggest that hydroxyl radicals may induce commitment of HL-60 cells to differentiate into more mature cells of myelomonocytic lineage through specific signal-transduction pathway that is modulated by phosphodiesterase inhibitors.

• Archives of Pharmacal Research
• /
• v.22 no.2
• /
• pp.202-207
• /
• 1999

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is ap preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with studies with synthetic compounds will be discussed in detail.

• 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.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.348.1-348.1
• /
• 2002

We synthesized various catechol ether type derivatives substituted by the hydrazine moiety and evaluated for their ability to inhibit PDE Ⅳ (Phosphodiesterase Ⅳ). These new compounds were synthesized from 4-methoxy-3-hydroxy benzaldehyde through 5 or 7 steps. Some of them have similar or more potent inhibitory activity against PDE Ⅳ than known PDE Ⅳ inhibitor. Ariflo (SB 207499). Structure activity relationship (SAR) and biological studies of described compounds will be discussed in detail. (omitted)

• Natural Product Sciences
• /
• v.23 no.3
• /
• pp.169-174
• /
• 2017

The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin ($10^{-7}$, $10^{-6}$, $10^{-5}$ and $10^{-4}M$). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.