• 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.

• 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.

• 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.

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.11 no.5
• /
• pp.402-407
• /
• 2006

Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

• The World Journal of Men's Health
• /
• v.39 no.3
• /
• pp.541-549
• /
• 2021

Purpose: To determine if chronic administration of Jun-amino terminal kinase (JNK)-inhibitors and LIM-kinase 2 (LIMK2)-inhibitors from the immediate post-injury period in a rat model of cavernous-nerve-crush-injury could normalize cavernousveno-occlusive-function, and to compare it with phosphodiesterase type 5 (PDE5)-inhibitors. Materials and Methods: A total of 75 12-week-old male Sprague-Dawley-rats were randomized into five groups: sham-surgery (S), cavernous-nerve-crush-injury (I), cavernous-nerve-crush-injury treated with 10.0 mg/kg LIMK2-inhibitor (L) or 10.0 mg/kg JNK-inhibitor and 10.0 mg/kg LIMK2-inhibitor (J+L) or 20.0 mg/kg udenafil (P) for five-weeks. Five-weeks after surgery, dynamic-infusion-cavernosometry, histological-studies, caspase-3-activity-assay, and Western-blot were investigated. Results: Group-I had lower papaverine-response, higher maintenance-rate and higher drop-rate, compared to Group-S. Group-L, Group-J+L and Group-P showed improvement in the three dynamic-infusion-cavernosometry parameters. The papaverine-response and drop-rate in Group-J+L and Group-P recovered to sham-control level, but those in Group-L did not. Regarding apoptosis, Group-I had decreased content of α-smooth-muscle-actin, increased caspase-3 activity and increased cJun-phosphorylation. The cJun-phosphorylation improved only in Group-J+L. The α-smooth-muscle-actin content and caspase-3-activity in Group-J+L and Group-P improved, but those in Group-L were not. Regarding fibrosis, Group-I had decreased smooth muscle (SM)/collagen-ratio, increased protein-expression of fibronectin, and increased Cofilin-phosphorylation. Cofilin-phosphorylation was normalized in Group-L and Group-J+L, but not in Group-P. SM/collagen-ratio and proteinexpression of fibronectin in Group-L, Group-J+L and Group-P improved. Conclusions: Our data indicate that chronic inhibition of JNK and LIMK2 can restore cavernous-veno-occlusive-function by suppressing cavernous-apoptosis and cavernous-fibrosis, comparable to the results by PDE5-inhibitors. Chronic inhibition of JNK and LIMK2 might be a potential mechanism-specific targeted therapy for cavernous-veno-occlusive-dysfunction induced by cavernous nerve-injury.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.2
• /
• pp.139-146
• /
• 2001

L-type $Ca^{2+}$ channels play an important role in regulating cytosolic $Ca^{2+}$ and thereby regulating hormone secretions in neuroendocrine cells. Since hormone secretions are also regulated by various kinds of protein kinases, we investigated the role of some kinase activators and inhibitors in the regulation of the L-type $Ca^{2+}$ channel currents in rat pituitary $GH_3$ cells using the patch-clamp technique. Phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator, and vanadate, a protein tyrosine phosphatase (PTP) inhibitor, increased the $Ba^{2+}$ current through the L-type $Ca^{2+}$ channels. In contrast, bisindolylmaleimide I (BIM I), a PKC inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, suppressed the $Ba^{2+}$ currents. Forskolin, an adenylate cyclase activator, and isobutyl methylxanthine (IBMX), a non-specific phosphodiesterase inhibitor, reduced $Ba^{2+}$ currents. The above results show that the L-type $Ca^{2+}$ channels are activated by PKC and PTK, and inhibited by elevation of cyclic nucleotides such as cAMP. From these results, it is suggested that the regulation of hormone secretion by various kinase activity in $GH_3$ cells may be attributable, at least in part, to their effect on L-type $Ca^{2+}$ channels.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.34 no.5
• /
• pp.215-221
• /
• 2020

Adulterated herbal medicine is intentionally added with undeclared improper or inferior ingredients which should not be in herbal medicine. The contamination with potentially hazardous substances such as heavy metal, pesticides, fungus, and microorganism sometimes can be regarded as one of adulteration in a broad sense. The problem of adulteration is that adulterated herbal medicine shows poor quality and/or can cause adverse events. Therefore, it is important to control adulteration issues for quality assurance and qualitative improvement of herbal medicines. This study aims to summarize and make a reference how to control adulterated herbal medicine. In this process, this study is to investigate studies about adulterated herbal medicine via searching Korean and foreign electronic databases such as PubMed, NDSL and OASIS. Finally eighteen papers were included to this study and analyzed according to the type of study, the category and efficacy of adulterants, the type of analysis methodologies and possible adverse events of adulterants. Phosphodiesterase type 5 (PDE-5) inhibitors for male sexual enhancement and anorexic, laxative, diuretic agents for weight loss and treating obesity has been used frequently as adulterants. The range of adverse event caused by adulterated herbal medicine were very wide from mild symptoms such as diarrhea, constipation, dizziness and blurred vision to very severe symptoms such as heart failure, hypoglycemia and renal impairment. This study showed the recent trend on the research of adulterated herbal medicine and this will be the ground to develop more detailed systems to control adulterated herbal medicine.

• Analytical Science and Technology
• /
• v.28 no.4
• /
• pp.278-287
• /
• 2015

Phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) are used in the treatment of erectile dysfunction. In recent years, a number of reports have been conducted on dietary supplements contaminated with PDE-5 analogues. In this study, 58 analogues of PDE-5 inhibitors were sorted into five groups: tadalafil, sildenafil, hongdenafil, vardenafil, and other analogues. These analogues were then evaluated using a liquid chromatography-quadrupole-time of flight mass spectrometry (LC-QTOF-MS) electrospray ionization mass method. Each compound has a unique fragmentation ion, which can be easily analyzed qualitatively. The fragmentation pathways of the analogues were elucidated based on the QTOF-MS and MS/MS data. Common ions were confirmed for each group by analyzing the structural characteristics and fragmentation pathways. Specifically, common ions were observed at m/z 169.08 and 135.04 (tadalafil analogues), m/z 311.15 and 283.12 (sildenafil analogues and hongdenafil analogues), and m/z 312.16 and 151.09 (vardenafil analogues). The advantage of this method is that the structure of unknown components can be determined by interpreting the product ions. Hence, the developed method can be used for the identification of unknown compounds. Fragmentation pathways may also aid in the detection and identification of PDE-5 inhibitor analogues.