Since sildenafil's (Viagra®), a phospodiesterase type 5 (PDE5) inhibitor, approval for the treatment of male erectile dysfunction (MED) in the United States early 1998, 274 adverse event reports were filed by the Food and Drug Administration (FDA) between 4 Jan. 1998 and 21 Feb. 2001 with sildenafil as the primary suspect of various neurological disturbances, including amnesia and aggressive behaviour (Milman and Arnold, 2002). These and other research findings have prompted investigations into the possible central effects of sildenafil. The G protein-coupled muscarinic adetylcholine receptors (mAChRs) and serotonergic receptors (5HT-Rs), have been linked to antidepressant action (Brink et al. 2004). GPCRs signal through the phosphatidylinositol signal transduction pathway known to activate protein kinases (PKs). Since the nitric oxide (NO)-guanylyl cyclase signal transduction pathway is also known to involve the activation of PKs (via cyclic guanosine monophosphate (cGMP)), the scope is opened for sildenafil to possibly modulate the action of antidepressants by elevating cGMP levels. It is generally assumed that excitotoxic delayed cell death is pathologically linked to an increase in the release of excitatory neurotransmitters e.g. glutamate. Glutamate antagonists, especially those that block the define NMDA-receptors, are neuroprotective, showing the importance of the NMDA-NO-cGMP pathway in neuroprotection (Brandt et al., 2003). Sildenafil may play a role in neuroprotection by elevating cGMP levels. Aims: The aims of the study were to investigate any neuroprotective properties of sildenafil, as well as modulating effects of sildenafil pre-treatment on mAChR function. Methods: Human neuroblastoma SH-SY5Y or human epithelial HeLa cells were seeded in 24-well plates and pre-treated for 24 hours in serum-free medium with no drug (control), PDE5 inhibitors sildenafil (100nM and 450 nM), dipiridamole (20 µM) or zaprinast (20 µM), non-selective PDE inhibitor 3-isobutyl-I-methylxanthine (IBMX - ImM), cGMP analogue N2,2'-0-dibutyrylguanosine 3'5'-cyclic monophosphate sodium salt (500 µM), guanylcyclase inhibitor 1H-[1 ,2,4]oxadiazolo[4,3-a]quinoxalin-I-one (ODQ - 3 µM) or sildenafil + ODQ (450 nM and 3 µM respectively). Thereafter cells were used to determine mAChR function by constructing dose-response curves of methacholine or to determine cell viability utilising the Trypan blue, propidium iodide and MTT tests for cell viability. Results: Sildenafil pre-treatments induced a 2.5-fold increase in ,the Emax value of methacholine in neuronal cells but did not show a significant increase in epithelial cells The Trypan blue test suggests that neither the PDE5 inhibitors nor a cGMP analogue show any neuroprotection. Rather, sildenafil 450 nM, dipiridamole and IBMX displayed a neurodegenerative effect. The MTT test was not suitable, since pre-treatment with the abovementioned drugs inhibited the formation of forrnazan. The propidium iodide assay could also not be used, due to severe cell loss. Conclusion: Sildenafil upregulates mAChR function in SH-SY5Y cells and displays a neurodegenerative, and not a protective property, in neuronal cells. This is not likely to be associated with its PDE5 inhibitory action, but may possibly be linked to an increase in cGMP levels via the NO-cGMP pathway. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

A necessidade de buscar novos tratamento para a Insuficiência Cardíaca (IC) crônica levanta o questionamento da eficácia e segurança de drogas que não foram adequadamente testadas ou que ainda não tiveram sua eficácia aceita pela comunidade científica. O sildenafil é um vasodilatador com potencial eficácia na redução da pressão sistólica da artéria pulmonar (PSAP), mas com pequenos estudos e sem demonstração de impacto em desfechos duros. Os diuréticos de alça são utilizados rotineiramente em pacientes com IC sem sinais de congestão e tal prática não está recomendada nas diretrizes terapêuticas, desconhecemos sua eficácia e segurança neste cenário. No intuito de elucidar estas questões, foram desenvolvidos I) revisão sistemática com metanálise para estudo uso de sildenafil. II) revisão sistemática com metanálise para estudo uso de diurético de alça, III) Delineamento e execução em andamento de ensaio clínico randomizado multicêntrico testando a retirada de diurético de alça. I e II) Métodos e resultados: Ambas revisões sistemáticas foram realizadas no Pubmed, Embase e Cochrane, e termos relacionados à insuficiência cardíaca crônica diurético de alça e sildenafil foram utilizados, respectivamente. Após avaliação de texto completo, apenas estudos em humanos foram incluídos na metanálise. A droga sildenafil foi avaliada em 9 estudos randomizados contra placebo e demonstrou redução de hospitalização (RR 0.29, 95% C.I 0.11 to 0.78) e melhora progressiva em parâmetros funcionais e hemodinâmicos O uso de diurético de alça foi testado em 7 ensaios clínicos e não mostrou significância em piora da função renal, distúrbio eletrolítico e mudança de peso. III) Métodos e resultados: Em um estudo duplo-cego randomizado, de não inferioridade, multicêntrico compara-se o a segurança e tolerabilidade da retirada de furosemida de pacientes com IC crônica e estável com disfunção ventricular. Com início da coleta em setembro de 2015, até o momento 96 pacientes foram randomizados. Conclusão: Quanto ao sildenafil, já temos evidências que apontam para um efeito benéfico e progressivo na melhora da capacidade funcional, perfil hemodinâmico e redução de hospitalização em pacientes com IC com disfunção ventricular e pressão da artéria pulmonar elevada A recomendação para uso de diurético de alça em pacientes estáveis com IC permanece uma incógnita e o ensaio clínico em andamento nos trará uma resposta de importante impacto clínico na tomada de decisão para manutenção do uso de diurético. / The challenges and promises of new treatments for chronic heart failure (CHF) raises the question of the efficacy and safety of drugs that have not been properly tested or that have not yet had their efficacy accepted by the scientific community. Sildenafil is a vasodilator with potential efficacy in reducing pulmonary artery systolic pressure (PSAP), but with small studies and no demonstration of impact on hard outcomes. Routinely, Loop diuretics are used in patients with HF without signs of congestion and such practice is not recommended in the therapeutic guidelines, we do not know its efficacy and safety in this scenario. In order to elucidate these questions, I) systematic review with meta-analysis were developed to study the use of sildenafil. II) systematic review with meta-analysis to study the use of loop diuretics, III) Design and execution in progress of a multicenter randomized clinical trial testing for loop diuretic withdrawal. I and II) Methods and results: Both systematic reviews were performed in PubMed, Embase and Cochrane, and terms related to chronic diuretic heart failure of the loop and sildenafil were used, respectively. After full-text evaluation, only human studies were included in the meta-analysis. The drug sildenafil was evaluated in 9 randomized placebo-controlled studies and demonstrated a reduction in hospitalization (RR 0.29, 95% CI 0.11 to 0.78) and progressive improvement in functional and hemodynamic parameters. The use of a loop diuretic was tested in 7 clinical trials and did not show significant deterioration in renal function, electrolyte disturbance and weight change. III. METHODS AND RESULTS: In a double-blind randomized, non-inferiority, multicenter study, the safety and tolerability of furosemide withdrawal from patients with chronic and stable HF with ventricular dysfunction were compared. Randomization started at September 2015, to the moment 96 patients were randomized. CONCLUSION: Regarding sildenafil, we already have evidence of a beneficial and time-related effect on the improvement of functional capacity, hemodynamic profile and reduction of hospitalization in patients with HF with ventricular dysfunction and elevated pulmonary artery pressure. The recommendation for the use of a loop diuretic in stable patients with HF remains an unknown and the ongoing clinical trial will provide us with an important clinical impact response in the decision making to maintain the use of diuretics.

A necessidade de buscar novos tratamento para a Insuficiência Cardíaca (IC) crônica levanta o questionamento da eficácia e segurança de drogas que não foram adequadamente testadas ou que ainda não tiveram sua eficácia aceita pela comunidade científica. O sildenafil é um vasodilatador com potencial eficácia na redução da pressão sistólica da artéria pulmonar (PSAP), mas com pequenos estudos e sem demonstração de impacto em desfechos duros. Os diuréticos de alça são utilizados rotineiramente em pacientes com IC sem sinais de congestão e tal prática não está recomendada nas diretrizes terapêuticas, desconhecemos sua eficácia e segurança neste cenário. No intuito de elucidar estas questões, foram desenvolvidos I) revisão sistemática com metanálise para estudo uso de sildenafil. II) revisão sistemática com metanálise para estudo uso de diurético de alça, III) Delineamento e execução em andamento de ensaio clínico randomizado multicêntrico testando a retirada de diurético de alça. I e II) Métodos e resultados: Ambas revisões sistemáticas foram realizadas no Pubmed, Embase e Cochrane, e termos relacionados à insuficiência cardíaca crônica diurético de alça e sildenafil foram utilizados, respectivamente. Após avaliação de texto completo, apenas estudos em humanos foram incluídos na metanálise. A droga sildenafil foi avaliada em 9 estudos randomizados contra placebo e demonstrou redução de hospitalização (RR 0.29, 95% C.I 0.11 to 0.78) e melhora progressiva em parâmetros funcionais e hemodinâmicos O uso de diurético de alça foi testado em 7 ensaios clínicos e não mostrou significância em piora da função renal, distúrbio eletrolítico e mudança de peso. III) Métodos e resultados: Em um estudo duplo-cego randomizado, de não inferioridade, multicêntrico compara-se o a segurança e tolerabilidade da retirada de furosemida de pacientes com IC crônica e estável com disfunção ventricular. Com início da coleta em setembro de 2015, até o momento 96 pacientes foram randomizados. Conclusão: Quanto ao sildenafil, já temos evidências que apontam para um efeito benéfico e progressivo na melhora da capacidade funcional, perfil hemodinâmico e redução de hospitalização em pacientes com IC com disfunção ventricular e pressão da artéria pulmonar elevada A recomendação para uso de diurético de alça em pacientes estáveis com IC permanece uma incógnita e o ensaio clínico em andamento nos trará uma resposta de importante impacto clínico na tomada de decisão para manutenção do uso de diurético. / The challenges and promises of new treatments for chronic heart failure (CHF) raises the question of the efficacy and safety of drugs that have not been properly tested or that have not yet had their efficacy accepted by the scientific community. Sildenafil is a vasodilator with potential efficacy in reducing pulmonary artery systolic pressure (PSAP), but with small studies and no demonstration of impact on hard outcomes. Routinely, Loop diuretics are used in patients with HF without signs of congestion and such practice is not recommended in the therapeutic guidelines, we do not know its efficacy and safety in this scenario. In order to elucidate these questions, I) systematic review with meta-analysis were developed to study the use of sildenafil. II) systematic review with meta-analysis to study the use of loop diuretics, III) Design and execution in progress of a multicenter randomized clinical trial testing for loop diuretic withdrawal. I and II) Methods and results: Both systematic reviews were performed in PubMed, Embase and Cochrane, and terms related to chronic diuretic heart failure of the loop and sildenafil were used, respectively. After full-text evaluation, only human studies were included in the meta-analysis. The drug sildenafil was evaluated in 9 randomized placebo-controlled studies and demonstrated a reduction in hospitalization (RR 0.29, 95% CI 0.11 to 0.78) and progressive improvement in functional and hemodynamic parameters. The use of a loop diuretic was tested in 7 clinical trials and did not show significant deterioration in renal function, electrolyte disturbance and weight change. III. METHODS AND RESULTS: In a double-blind randomized, non-inferiority, multicenter study, the safety and tolerability of furosemide withdrawal from patients with chronic and stable HF with ventricular dysfunction were compared. Randomization started at September 2015, to the moment 96 patients were randomized. CONCLUSION: Regarding sildenafil, we already have evidence of a beneficial and time-related effect on the improvement of functional capacity, hemodynamic profile and reduction of hospitalization in patients with HF with ventricular dysfunction and elevated pulmonary artery pressure. The recommendation for the use of a loop diuretic in stable patients with HF remains an unknown and the ongoing clinical trial will provide us with an important clinical impact response in the decision making to maintain the use of diuretics.

Chronic damage to pulmonary vessels leads to pulmonary hypertension (PH). Different forms of PH are quite frequent and are associated with significant morbidity and mortality. The treatment of PH is most successful, if its cause can be identified and removed before irreversible damage to the pulmonary vascular bed occurs. For patients, in whom the elimination of the underlying cause is not possible or where the cause is unknown, the treatment is aimed at reduction of pulmonary vascular resistance and improvement of cardiac and circulatory response to pressure overload of the right ventricle. One option for the PH treatment is modification of metabolism of cyclic guanosine monophosphate (GMP), which is the second messenger of nitric oxide and induces vascular vasodilation. Cyclic GMP is degraded by phosphodiesterases (PDE 5). In the clinical part, we tested the hypothesis that acute inhibition of PDE5 by sildenafil provides more selective pulmonary vasodilation than high doses of prostaglandin E1 (PGE1). The study showed that the vasodilator effects of sildenafil on pulmonary circulation is more pronounced than in the systemic circulation and that sildenafil had a greater ability to detect reversible component precapillary PH due to advanced chronic heart failure than PGE1. The aim of our...

Submitted by Cibele Nogueira (cibelenogueira@ufgd.edu.br) on 2016-04-15T14:57:19Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) BRUNAARANHA.pdf: 8666505 bytes, checksum: 54c9fbf95f7882748fed8e4968abd5c7 (MD5) / Made available in DSpace on 2016-04-15T14:57:19Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) BRUNAARANHA.pdf: 8666505 bytes, checksum: 54c9fbf95f7882748fed8e4968abd5c7 (MD5) Previous issue date: 2015-02-26 / Over the past few years, the search for materials that can be used in industrial applications has been growing exponentially. Among these, we can mention the polymeric materials, which are being used to replace different classic raw materials, such as glass, ceramics, wood and metal. Among the most important applications can be cited using the optical industry, electronics, petrochemical and pharmaceutical industries. In this context, the present study aims to study different materials: synthesis and optical characterization of poly (fluoride) doped with holmium vinylidene complex and the comparative study of different tablets of 50 mg of sildenafil citrate marketed in Brazil and Paraguay through optical fluorescence spectroscopy technique, in order to show that this technique is useful for identifying different organic molecules such as drugs and medicines. PVDF samples were characterized by spectroscopy in the infrared (FT-IR) spectroscopy, UV-vis absorption (UV-Vis) and fluorescence spectroscopy (EF). To study samples of 50 mg of sildenafil have been used FT-IR techniques, UVVis and EF. The experimental results showed that the route synthesis of PVDF film was adequate, since the films obtained were homogenous and translucent. With increasing relative phase beta fraction of PVDF and band widening of the fluorescence, the samples obtained are candidates for potential technological applications. For sildenafil samples we observed significant differences between the samples. Thus, it can be inferred that the techniques used are potential candidates for the study medications. However, for an application of these techniques for this purpose, further studies are needed and the construction of a calibration curve. / Ao longo dos últimos anos, a busca por materiais que possam ser utilizados em aplicações industriais vêm crescendo exponencialmente. Dentre esses, podemos citar os materiais poliméricos, que estão sendo utilizados na substituição de diferentes matérias primas clássicas, como vidros, cerâmicas, madeiras e metais. Entre as aplicações mais importantes podem ser citadas a utilização na indústria óptica, eletrônica, petroquímica e farmacêutica. Neste contexto, o presente trabalho objetiva o estudo das técnicas espectroscópicas para a caracterização de diferentes materiais, como o polímero poli(fluoreto) de vinilideno (PVDF) dopado com óxido de hólmio, hólmio complexado com o ligante 2-aminoreftalato e somente com o ligante e comprimidos de 50 mg de citrato de sildenafila comercializados no Brasil e Paraguai. As amostras de PVDF foram caracterizadas por espectroscopia na região do infravermelho (FT-IR), espectroscopia de absorção UV-vis (UV-Vis) e espectroscopia de fluorescência (EF). Para estudo das amostras de sildenafil 50 mg foram utilizadas as técnicas de FT-IR, UV-Vis e EF. Os resultados experimentais mostraram que a rota de síntese dos filmes de PVDF foi adequada, uma vez que os filmes obtidos apresentaram-se homogêneos e translúcidos. De acordo com os resultados obtidos, foi possível observar que as técnicas espectroscópicas são sensíveis e de extrema valia para caracterizar as amostras obtidas. Para os comprimidos de sildenafil 50 mg foi possível observar diferenças significativas entre as amostras analisadas, mostrando que as técnicas utilizadas são candidatas em potencial para o estudo de medicamentos. Porém, para uma aplicação destas técnicas para essa finalidade, são necessários estudos mais detalhados, bem como a construção de uma curva de calibração.

Orientador: Heitor Moreno Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T22:07:27Z (GMT). No. of bitstreams: 1 Silva_ThiagoQuinagliaAraujoCosta_D.pdf: 1420649 bytes, checksum: e60823c9257fdc54d91d49f992550d11 (MD5) Previous issue date: 2013 / Resumo: Objetivo: A falha no controle da pressão arterial (PA), apesar do uso de três ou mais antihipertensivos caracteriza hipertensão arterial resistente (HAR). A disfunção endotelial está intrinsecamente associada a esta condição e inibidores da fosfodiesterase 5 (iPDE5)-inibindo a degradação de GMP cíclico (GMPc)-reduzem a PA em pacientes com HAR. A administração aguda de iPDE5 poderia melhorar parâmetros hemodinâmicos, endoteliais e de função diastólica do ventrículo esquerdo (FDVE) em pacientes com HAR e o polimorfismo T-786C da sintase de óxido nítrico (NO) endotelial (eNOS) modularia essas respostas. Métodos: Os pacientes (n = 26) foram dispostos em três grupos de acordo com o genótipo da eNOS T-786C: CC (n = 8), a CT (n = 9) e TT (n = 9). Doses crescentes de sildenafil oral (37,5, 50 e 100 mg) e placebo (em datas separadas por pelo menos 2 semanas) foram administradas a intervalos de 30 minutos, enquanto parâmetros hemodinâmicos (não invasivos e contínuos) foram obtidos. Também foram determinados: FDVE; vasodilatação mediada por fluxo (VMF); e nitrito e GMPc plasmáticos ao início e término do protocolo. Resultados: PA média (PAM) e resistência periférica total (RPT) diminuíram no grupo total (n=26) após o sildenafil (84,17 ± 21,04-75 ± 17,21 mmHg, 1149 ± 459,7-1,037 dyn.s/cm-5 ± 340, respectivamente; p<0,05). Similarmente, o sildenafil melhorou a FDVE (volume atrial esquerdo: 25 ± 5,8-20 ± 4,4; Tempo de relaxamento isovolumétrico: 104 ± 19,33-88 ± 15,22; E/e'septal: 9,7 ± 3,8-7,9 ± 2,9; E/e' lateral: 7,7 ± 3,4-6,4 ± 3,2; p<0,05). Os grupos TT e TC obtiveram redução sustentada da RPT ao longo do protocolo. No CC, os valores da RPT retornaram aos basais após as doses. Não houve alterações significativas da VMF, nitrito e GMPc após a administração do sildenafil. Conclusão: A administração aguda de iPDE5 melhora o perfil hemodinâmico e função diastólica em HAR e o polimorfismo T-786C da eNOS modula a resposta hemodinâmica, mas não a FDVE / Abstract: Purpose: Failure to control blood pressure (BP) despite the use of three or more drugs characterizes resistant hypertension (RHTN). Impaired endothelial function is associated to this condition and phosphodiesterase-5 inhibitors (PDE5i)-inhibiting cGMP breakdown-reduce BP in RHTN patients. We hypothesized that acute administration of PDE5i could ameliorate hemodynamic, endothelial parameters and left ventricular diastolic function (LVDF) in RHTN patients and that the T-786C nitric oxide (NO) endothelial synthase (eNOS) polymorphism could modulate these responses. Methods: Subjects (n= 26) were arranged into three groups: CC (n= 8), TC (n= 9) and TT (n= 9) according to T-786C eNOS genotype. Increasing doses of oral sildenafil (37.5, 50 and 100 mg) and placebo (in protocols at least 2 weeks apart) were given at 30 minute intervals while continuous non-invasive hemodynamic measures were assessed. LVDF, Flow Mediated Dilation (FMD), plasma nitrite and cGMP were also determined. Results: Mean arterial pressure (MAP) and total peripheral resistance (RPT) decreased in all patients (84.17 ± 21.04 to 75 ± 17.21 mmHg; 1149 ± 459.7 to 1037 ± 340 dyn.s/cm-5, respectively; p<0.05). Likewise, sildenafil improved LVDF parameters (Left atrial volume: 25 ± 5.8 to 20 ± 4.4; Isovolumetric relaxation time: 104 ± 19.33 to 88 ± 15.22; E/e' septal: 9.7 ± 3.8 to 7.9 ± 2.9; E/e' lateral: 7.7 ± 3.4 to 6.4 ± 3.2; p<0.05). While TT and TC genotype groups sustained RPT reduction during the increasing sildenafil doses, CC group failed to sustain the RPT drop, by the end of the protocol. No statistical changes were found in FMD, nitrite and cGMP after PDE5i administration. Conclusion: Our data suggest PDE5i acutely improves hemodynamic profile and diastolic function in RHTN, also T-786C eNOS polymorphism modulates the hemodynamic response, but not diastolic function / Doutorado / Farmacologia / Doutor em Farmacologia

Chronic damage to pulmonary vessels leads to pulmonary hypertension (PH). Different forms of PH are quite frequent and are associated with significant morbidity and mortality. The treatment of PH is most successful, if its cause can be identified and removed before irreversible damage to the pulmonary vascular bed occurs. For patients, in whom the elimination of the underlying cause is not possible or where the cause is unknown, the treatment is aimed at reduction of pulmonary vascular resistance and improvement of cardiac and circulatory response to pressure overload of the right ventricle. One option for the PH treatment is modification of metabolism of cyclic guanosine monophosphate (GMP), which is the second messenger of nitric oxide and induces vascular vasodilation. Cyclic GMP is degraded by phosphodiesterases (PDE 5). In the clinical part, we tested the hypothesis that acute inhibition of PDE5 by sildenafil provides more selective pulmonary vasodilation than high doses of prostaglandin E1 (PGE1). The study showed that the vasodilator effects of sildenafil on pulmonary circulation is more pronounced than in the systemic circulation and that sildenafil had a greater ability to detect reversible component precapillary PH due to advanced chronic heart failure than PGE1. The aim of our...

No / Cortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex, and may contribute to the pathophysiology of stroke and migraine. Previous studies demonstrated that nitric oxide (NO) formation promotes the repolarisation phase of CSD, and this effect may be cyclic GMP (cGMP)-mediated. Here, we have examined how phosphodiesterase (PDE) inhibition, either alone or superimposed on NO synthase (NOS) inhibition, alters CSD and the associated changes in extracellular cGMP. Microdialysis probes incorporating an electrode were implanted into the frontoparietal cortex of anaesthetised rats for quantitative recording of CSD, pharmacological manipulations, and dialysate sampling for cGMP measurements. CSD was induced by cathodal electrical stimulation in the region under study by microdialysis. Extracellular cGMP increased, but only slightly, during CSD. Perfusion of either zaprinast or sildenafil through the microdialysis probe, at concentrations that inhibited both PDE5 and PDE9 (and possibly other PDE), increased significantly extracellular cGMP. Unexpectedly, these levels remained high when NOS was subsequently inhibited with N¿-nitro- -arginine methyl ester hydrochloride ( -NAME, 1 mM). The most interesting pharmacological effect on CSD was obtained with sildenafil. This drug altered neither CSD nor the subsequent characteristic effect of NOS inhibition, i.e. a marked widening of CSD. The fact that NOS inhibition still widened CSD in the presence of the high extracellular levels of cGMP associated with PDE inhibition, suggests that NO may promote CSD recovery, independently of cGMP formation.

Yes / New multicomponent solid forms of sildenafil have been discovered by means of a combined virtual/experimental cocrystal screening. Coformer selection of candidates was conducted based on an in silico screening method from a database of more than 2000 organic compounds, and the intensive experimental screen produced 23 new solid forms. Since the 12 coformers chosen have a combination of phenol and carboxylic acid groups, a variety of cocrystals, salts, and hybrid salt-cocrystals were discovered and characterized.

This diploma thesis is focused on the determination of phosphodiesterase 5 selective inhibitors in communal waste waters. In this study phosphodiesterase inhibitors levels in municipal waste waters from sewage treatment plants with different numbers of equivalent inhabitants were analyzed. Namely it was sewage treatment plants in Brno – Modřice, Luhačovice and Hodonín. In each of the above mentioned facilities 24 - hour cumulated samples of the influent and effluent waste water were collected. On the Brno - Modřice sewage treatment plant also weekly monitoring of the concentration of phosphodiesterase inhibitors was realized.