Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neurop...Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neuropathy,展开更多
A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data...A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data, and the PDE5 inhibitory activities of the target compounds. The polar piperazinyl group contained （on 5＇-position） compound, 3B2, showed the highest activity among the tested derivatives but less potency than sildenafil 1.展开更多
Counterfeit medicines are a growing problem in both developing and industrialised countries. In general the evaluation of these medicines is limited to the identification and the dosage of the active ingredients. In t...Counterfeit medicines are a growing problem in both developing and industrialised countries. In general the evaluation of these medicines is limited to the identification and the dosage of the active ingredients. In this study in vitro dissolution tests were conducted on two sets of counterfeit medicines containing PDE-5 inhibitors （sildenafil citrate and tadalafil）. The dissolution profiles were statistically compared to the ones of the genuine products using the f2-method and a comparison at each time point using the Cochran test. The results showed low equivalences between counterfeit and genuine products as well as higher variations around the mean dissolution value at the different time points for the counterfeit products.展开更多
目的将实时直接分析离子源(direct analysis in real time,DART)与三重四极杆质谱联用,建立食品中非法添加PDE-5型抑制剂的快速筛查方法。方法3种不同基质样品加入乙腈振摇10 s后,设进样速率0.2 mm/s,进样体积4μl,选择DART离子源,离子...目的将实时直接分析离子源(direct analysis in real time,DART)与三重四极杆质谱联用,建立食品中非法添加PDE-5型抑制剂的快速筛查方法。方法3种不同基质样品加入乙腈振摇10 s后,设进样速率0.2 mm/s,进样体积4μl,选择DART离子源,离子化温度450℃,在正离子、多反应监测(MRM)下进行检测。结果该方法7种物质的检出限为0.025~12.5μg/g,检出阳性样品4种,分别非法添加羟基卡巴地那非、环己基去甲他达拉非、N-苄基他达拉非和N-苯基丙氧苯基卡巴地那非。结论该方法样品前处理简单,分析速度快,定性准确,环境污染小,能满足食品中非法添加PDE-5型抑制剂的快速筛查要求。展开更多
Chronic exposure to drugs of abuse will give rise to persistent structural and functional changes in the central nervous system. These phenomena are usually referred as ′drug-induced neuroplasticity′ and depend on c...Chronic exposure to drugs of abuse will give rise to persistent structural and functional changes in the central nervous system. These phenomena are usually referred as ′drug-induced neuroplasticity′ and depend on changes in gene expression. The cAMP response element binding protein(CREB),as a downstream molecule in mediating the actions of cAMP is an important transcriptional factor in establishing and maintaining addiction to drugs of abuse. Application of a PDE4 inhibitor attenuates the rewarding properties of cocaine and morphine. Given the fact that PDE10A is specifically located in striatum,an important structure involved in the reward circuit,we thus investigated the PDE10A inhibitormodulated the behavioral reinforcement exerted by morphine. The results show that MP-10 2.5 mg·kg^(-1),administered subcutaneously,significantly inhibited the acquisition of morphine-induced CPP. Moreover,MP-10 did not alter the expression of morphine-induced CPP,but did accelerate the extinction of morphine-induced CPP. Additionally,chronic treatment with MP-10 2.5 mg·kg^(-1)decreased expression of phosphorylated CREB(pC REB) in dorsomedial striatum,in shell of NAc,and in anterior cingulate cortex(ACC) as well as decreased expression of ΔFos B in the shell of NAc and ACC. These data indicate that PDE10A inhibition may have a potential therapeutic effect on addiction. Since the MP-10 has relative short metabolic Stability,we also developed a few novel potent new PDE10A selective inhibitor with improved stability and brain exposure. The new compound exhibited promising potential in schizophrenia and addiction treatment.展开更多
Erectile dysfunction(ED)is a common male disorder.Although orally-administered phosphodiesterase type 5 inhibitors(PDE5 inhibitors)are now recognized as the primary pharmacological treatment method for ED,20%-30%of th...Erectile dysfunction(ED)is a common male disorder.Although orally-administered phosphodiesterase type 5 inhibitors(PDE5 inhibitors)are now recognized as the primary pharmacological treatment method for ED,20%-30%of the patients treated with PDE5 inhibitors exhibit no significant effects.This study aims to investigate the influencing factors of ED in young adults with no response to PDE5 inhibitors.ED patients who would take PDE5 inhibitors were included and investigated with a questionnaire.Patients with no response to PDE5 inhibitors(tadalafil and sildenafil)served as study group,and those with response to PDE5 inhibitors as control group.Then Chi square test and logistic regression analysis were applied to find the potential influencing factors.In total,378 ED patients were included.Ninety-three(24.6%)cases were non-responsive to PDE5 inhibitors,and the remaining 285(75.4%)responded to PDE5 inhibitors.In multiple logistic regression analysis,we found that history of drinking(OR=3.152;95%CI 1.672-6.975),spousal noncooperation(OR=2.994;95%CI 1.589-5.638),number of fixed sex partners(OR=0.358;95%CI 0.132-0.651),duration of ED(OR=3.356;95%CI 1.352-8.333),and depression(OR=3.689;95%CI 1.579-8.979)could be the influencing factors for ED patients’non-response to PDE5 inhibitors.In conclusion,history of drinking,spousal noncooperation,number of fixed sex partner,long duration of ED,and depression could be the influencing factors for ED patients'non-response to PDE5 inhibitors.Patients and doctors should pay attention to these factors.展开更多
The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction （ED） treated with phosphodiesterase type 5 inhibitors （PDE-5i） over a 7-year period vs. men with...The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction （ED） treated with phosphodiesterase type 5 inhibitors （PDE-5i） over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups： 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 （4.1%） men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 （9.9%） men with ED in the non-treated group （P〈00001）. A higher percentage of African Americans were treated with PDE-5i vs. those who were not （10.5% vs. 7.1%; P〈O.O001）. The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen （10.0% vs. 13.1%; P=-0.0008） and higher percentage of benign prostatic hyperplasia （38.4% vs. 35.1%; P=0.0149）. Men with ED treated with PDE-5i tended to have less chance （adjusted odds ratio： 0.4; 95% confidence intervals： 0.3-0.5; P〈0.0001） of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of beine diaenosed with orostate cancer. Further research is warranted.展开更多
建立了高效液相色谱串联质谱仪对酒类产品中11种PDE-5抑制剂及其衍生剂的快速分析方法。样品经乙腈∶水(1∶1,v/v)超声提取,Atlantis d C_(18)色谱柱(2.1×150 mm,3μm)为分析柱,0.1%甲酸溶液和0.1%甲酸乙腈为流动相,电喷雾正离子...建立了高效液相色谱串联质谱仪对酒类产品中11种PDE-5抑制剂及其衍生剂的快速分析方法。样品经乙腈∶水(1∶1,v/v)超声提取,Atlantis d C_(18)色谱柱(2.1×150 mm,3μm)为分析柱,0.1%甲酸溶液和0.1%甲酸乙腈为流动相,电喷雾正离子多反应监测模式进行检测,外标法定量。试验结果表明,该方法的RSD值范围为0.57%~11.69%,回收率范围在60.0%~118.6%,该方法的线性相关性良好,检测低限、精密度和准确度均符合要求,能够满足酒类产品中11种PDE-5抑制剂及其衍生剂的检测要求。展开更多
基金supported by NINDS grants RO1 NS075084(LW)NIDDK RO1 DK097519(LW)
文摘Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neuropathy,
文摘A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data, and the PDE5 inhibitory activities of the target compounds. The polar piperazinyl group contained （on 5＇-position） compound, 3B2, showed the highest activity among the tested derivatives but less potency than sildenafil 1.
文摘Counterfeit medicines are a growing problem in both developing and industrialised countries. In general the evaluation of these medicines is limited to the identification and the dosage of the active ingredients. In this study in vitro dissolution tests were conducted on two sets of counterfeit medicines containing PDE-5 inhibitors （sildenafil citrate and tadalafil）. The dissolution profiles were statistically compared to the ones of the genuine products using the f2-method and a comparison at each time point using the Cochran test. The results showed low equivalences between counterfeit and genuine products as well as higher variations around the mean dissolution value at the different time points for the counterfeit products.
文摘目的将实时直接分析离子源(direct analysis in real time,DART)与三重四极杆质谱联用,建立食品中非法添加PDE-5型抑制剂的快速筛查方法。方法3种不同基质样品加入乙腈振摇10 s后,设进样速率0.2 mm/s,进样体积4μl,选择DART离子源,离子化温度450℃,在正离子、多反应监测(MRM)下进行检测。结果该方法7种物质的检出限为0.025~12.5μg/g,检出阳性样品4种,分别非法添加羟基卡巴地那非、环己基去甲他达拉非、N-苄基他达拉非和N-苯基丙氧苯基卡巴地那非。结论该方法样品前处理简单,分析速度快,定性准确,环境污染小,能满足食品中非法添加PDE-5型抑制剂的快速筛查要求。
文摘Chronic exposure to drugs of abuse will give rise to persistent structural and functional changes in the central nervous system. These phenomena are usually referred as ′drug-induced neuroplasticity′ and depend on changes in gene expression. The cAMP response element binding protein(CREB),as a downstream molecule in mediating the actions of cAMP is an important transcriptional factor in establishing and maintaining addiction to drugs of abuse. Application of a PDE4 inhibitor attenuates the rewarding properties of cocaine and morphine. Given the fact that PDE10A is specifically located in striatum,an important structure involved in the reward circuit,we thus investigated the PDE10A inhibitormodulated the behavioral reinforcement exerted by morphine. The results show that MP-10 2.5 mg·kg^(-1),administered subcutaneously,significantly inhibited the acquisition of morphine-induced CPP. Moreover,MP-10 did not alter the expression of morphine-induced CPP,but did accelerate the extinction of morphine-induced CPP. Additionally,chronic treatment with MP-10 2.5 mg·kg^(-1)decreased expression of phosphorylated CREB(pC REB) in dorsomedial striatum,in shell of NAc,and in anterior cingulate cortex(ACC) as well as decreased expression of ΔFos B in the shell of NAc and ACC. These data indicate that PDE10A inhibition may have a potential therapeutic effect on addiction. Since the MP-10 has relative short metabolic Stability,we also developed a few novel potent new PDE10A selective inhibitor with improved stability and brain exposure. The new compound exhibited promising potential in schizophrenia and addiction treatment.
文摘Erectile dysfunction(ED)is a common male disorder.Although orally-administered phosphodiesterase type 5 inhibitors(PDE5 inhibitors)are now recognized as the primary pharmacological treatment method for ED,20%-30%of the patients treated with PDE5 inhibitors exhibit no significant effects.This study aims to investigate the influencing factors of ED in young adults with no response to PDE5 inhibitors.ED patients who would take PDE5 inhibitors were included and investigated with a questionnaire.Patients with no response to PDE5 inhibitors(tadalafil and sildenafil)served as study group,and those with response to PDE5 inhibitors as control group.Then Chi square test and logistic regression analysis were applied to find the potential influencing factors.In total,378 ED patients were included.Ninety-three(24.6%)cases were non-responsive to PDE5 inhibitors,and the remaining 285(75.4%)responded to PDE5 inhibitors.In multiple logistic regression analysis,we found that history of drinking(OR=3.152;95%CI 1.672-6.975),spousal noncooperation(OR=2.994;95%CI 1.589-5.638),number of fixed sex partners(OR=0.358;95%CI 0.132-0.651),duration of ED(OR=3.356;95%CI 1.352-8.333),and depression(OR=3.689;95%CI 1.579-8.979)could be the influencing factors for ED patients’non-response to PDE5 inhibitors.In conclusion,history of drinking,spousal noncooperation,number of fixed sex partner,long duration of ED,and depression could be the influencing factors for ED patients'non-response to PDE5 inhibitors.Patients and doctors should pay attention to these factors.
文摘The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction （ED） treated with phosphodiesterase type 5 inhibitors （PDE-5i） over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups： 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 （4.1%） men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 （9.9%） men with ED in the non-treated group （P〈00001）. A higher percentage of African Americans were treated with PDE-5i vs. those who were not （10.5% vs. 7.1%; P〈O.O001）. The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen （10.0% vs. 13.1%; P=-0.0008） and higher percentage of benign prostatic hyperplasia （38.4% vs. 35.1%; P=0.0149）. Men with ED treated with PDE-5i tended to have less chance （adjusted odds ratio： 0.4; 95% confidence intervals： 0.3-0.5; P〈0.0001） of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of beine diaenosed with orostate cancer. Further research is warranted.
文摘建立了高效液相色谱串联质谱仪对酒类产品中11种PDE-5抑制剂及其衍生剂的快速分析方法。样品经乙腈∶水(1∶1,v/v)超声提取,Atlantis d C_(18)色谱柱(2.1×150 mm,3μm)为分析柱,0.1%甲酸溶液和0.1%甲酸乙腈为流动相,电喷雾正离子多反应监测模式进行检测,外标法定量。试验结果表明,该方法的RSD值范围为0.57%~11.69%,回收率范围在60.0%~118.6%,该方法的线性相关性良好,检测低限、精密度和准确度均符合要求,能够满足酒类产品中11种PDE-5抑制剂及其衍生剂的检测要求。
