{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:56:07Z","timestamp":1791849367746,"version":"4.3.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"BIOZEUS"},{"name":"CNPq"},{"name":"CAPES"},{"DOI":"10.13039\/501100004933","name":"INCTTOX","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004933","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>With the aim of overcoming the high toxicity of PnTx2-6 (or \u03b4-CNTX-Pn2a), a toxin from the venom of the armed spider (Phoneutria nigriventer), the 19-aminoacid peptide, PnPP-19 (P nigriventer potentiator peptide), was synthesized based on molecular modeling studies of PnTx2-6. PnPP-19 improved the erectile function of normotensive rats and mice, without eliciting side effects, and no signs of toxicity were observed. In addition, PnPP-19 was able to potentiate the effect of sildenafil.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To evaluate the efficacy of PnPP-19 in hypertensive and diabetic mouse\/rat models in restoring erectile function, after topical administration; verify the biodistribution of PnPP-19 administration (topical and intravenous), permeation, and cyclic guanosine monophosphate (cGMP)\/nitric oxide via implication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Corpus cavernosum relaxation was evaluated using cavernous strips from male spontaneous hypertensive rats (SHR) and from streptozotocin (STZ)-diabetic mice contracted with phenylephrine and submitted to electrical field stimulation before and after incubation with PnPP-19 (10\u22128 mol\/L, 10 minutes) or vehicle. This procedure was also used to determine cGMP\/nitric oxide levels, at 8 Hz and to check the effect of PnPP-19 with sildenafil citrate. Biodistribution assays were performed using iodine 123\u2013radiolabeled PnPP-19. In\u00a0vivo erectile function was evaluated using intracavernosal pressure\/main arterial pressure ratio in STZ-diabetic rats after PnPP-19 topical administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>PnPP-19 may become a new drug able to fill the gap in the pharmacologic treatment of erectile dysfunction, especially for hypertensive and diabetic individuals<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PnPP-19 potentiated corpus cavernosum relaxation, in both control and SHR rats. SHR-cavernosal tissue treated with PnPP-19 (1\u201332 Hz) reached the same relaxation levels as control Wistar rats (16 and 32 Hz). PnPP-19 treatment improved cavernosal tissue relaxation in STZ-diabetic mice and rats. PnPP-19 enhanced cGMP levels in STZ-diabetic mice corpus cavernosum strips. After topical or intravenous administration in rats, 123I-PnPP-19 was mainly recruited to the penis. When topically administered (400 \u03bcg\/rat), PnPP-19 restores erectile function in STZ-diabetic rats, also improving it in healthy rats by increasing the intracavernosal pressure\/main arterial pressure ratio. PnPP-19 exhibited an additive effect when co-administered with sildenafil, showing a novel mode of action regardless of phosphodiesterase type 5 inhibition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Implications<\/jats:title>\n                  <jats:p>PnPP-19 seems to be an indicated drug to be tested to treat ED in diabetic and hypertensive patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strength &amp; Limitations<\/jats:title>\n                  <jats:p>PnPP-19, although active by topical application and showing safety to human beings (not shown), has low permeability, about 10% of the applied dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results showed that PnPP-19 may emerge as a potent new drug that can be topically administered, becoming a promising alternative for erectile dysfunction treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2019.01.004","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:14:41Z","timestamp":1550189681000},"page":"365-374","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration"],"prefix":"10.1093","volume":"16","author":[{"given":"Carolina","family":"Nunes da Silva","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Universidade Federal de Minas Gerais \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00eania Pedrosa","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Chemical Engineering and Sciences \u00a0 , Melbourne, FL , USA"},{"name":"Florida Institute of Technology \u00a0 , Melbourne, FL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"De Marco Almeida","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Universidade Federal de Minas Gerais \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Lucas","family":"Silva Costa","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Universidade Federal de Minas Gerais \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perla Villani","family":"Borges","sequence":"additional","affiliation":[{"name":"BIOZEUS Biopharmaceutical S.A. , Rio de Janeiro, RJ , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Lacativa","sequence":"additional","affiliation":[{"name":"BIOZEUS Biopharmaceutical S.A. , Rio de Janeiro, RJ , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano Monteiro C.","family":"Pimenta","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Universidade Federal de Minas Gerais \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Elena de Lima","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Universidade Federal de Minas Gerais \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade \u00a0 \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Biomedicina e Medicina \u00a0 \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Ensino e Pesquisa da Santa Casa de Belo Horizonte \u00a0 \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"},{"name":"Grupo Santa Casa de Belo Horizonte \u00a0 \u00a0 \u00a0 , Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"2023012309520145800_bib1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/14728214.2010.480973","article-title":"The future is today: Emerging drugs for the treatment of erectile dysfunction","volume":"15","author":"Albersen","year":"2010","journal-title":"Expert Opin Emerg Drugs"},{"key":"2023012309520145800_bib2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/j.1745-7254.2007.00584.x","article-title":"Neurophysiological basis of penile erection","volume":"28","author":"Priviero","year":"2007","journal-title":"Acta Pharmacol Sin"},{"key":"2023012309520145800_bib3","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/S0165-6147(00)01587-X","article-title":"Pharmacotherapy for erectile dysfunction. Review","volume":"21","author":"Bivalacqua","year":"2000","journal-title":"Trends Pharmacol Sci"},{"key":"2023012309520145800_bib4","doi-asserted-by":"crossref","first-page":"16003","DOI":"10.1038\/nrdp.2016.3","article-title":"Erectile dysfunction","volume":"2","author":"Yafi","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"2023012309520145800_bib5","first-page":"3","article-title":"Mechanisms in erectile function and dysfunction: An overview","volume":"Vol 1","author":"Nunes","year":"2012","journal-title":"Erectile dysfunction\u2013Disease associated mechanisms and novel insights into therapy"},{"key":"2023012309520145800_bib6","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.mcna.2010.08.016","article-title":"Evaluation and treatment of erectile dysfunction","volume":"95","author":"Albersen","year":"2011","journal-title":"Med Clin North Am"},{"key":"2023012309520145800_bib7","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2174\/1389450116666150427160710","article-title":"Emerging molecular targets\u00a0for treatment of erectile dysfunction: Vascular and regenerative therapies on the horizon","volume":"16","author":"Stallmann-Jorgensen","year":"2015","journal-title":"Curr Drug Targets"},{"key":"2023012309520145800_bib8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1001\/archinte.166.2.207","article-title":"Predictors and prevalence of erectile dysfunction in a racially diverse population","volume":"166","author":"Saigal","year":"2006","journal-title":"Arch Intern Med"},{"key":"2023012309520145800_bib9","article-title":"World health statistics 2012","year":"2012"},{"key":"2023012309520145800_bib10","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.2174\/138161209789206971","article-title":"PDE5 Inhibitors: In\u00a0vitro and in\u00a0vivo pharmacological profile","volume":"15","author":"Kouvelas","year":"2009","journal-title":"Curr Pharm Des"},{"key":"2023012309520145800_bib11","first-page":"445","article-title":"Anatomy, physiology, and pathophysiology of erectile dysfunction","volume":"7","author":"Gratzke","year":"2010","journal-title":"J\u00a0Sex Med"},{"key":"2023012309520145800_bib12","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1124\/pr.111.004515","article-title":"Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction","volume":"63","author":"Andersson","year":"2011","journal-title":"Pharmacol Rev"},{"key":"2023012309520145800_bib13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1074\/mcp.M900286-MCP200","article-title":"Molecular targets for diabetes mellitus-associated erectile dysfunction","volume":"9","author":"Yohannes","year":"2010","journal-title":"Mol Cell Proteomics"},{"key":"2023012309520145800_bib14","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1001\/jama.1996.03530440037034","article-title":"The progression from hypertension to congestive heart failure","volume":"275","author":"Levy","year":"1996","journal-title":"JAMA"},{"key":"2023012309520145800_bib15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0733-8651(02)00004-8","article-title":"The heart, kidney, and brain\u00a0as target organs in hypertension","volume":"20","author":"Mensah","year":"2002","journal-title":"Cardiol Clin"},{"key":"2023012309520145800_bib16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11886-017-0889-z","article-title":"Evaluation and management of erectile dysfunction in the hypertensive patient","volume":"19","author":"Patel","year":"2017","journal-title":"Curr Cardiol Rep"},{"key":"2023012309520145800_bib17","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1001\/archinte.1997.00440270080007","article-title":"Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study","volume":"157","author":"Grimm","year":"1997","journal-title":"Arch Intern Med"},{"key":"2023012309520145800_bib18","first-page":"856","article-title":"Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in patients with erectile dysfunction and arterial hypertension treated with multiple antihypertensives","volume":"2","author":"Van Ahlen","year":"2005","journal-title":"J\u00a0Sex Med"},{"key":"2023012309520145800_bib19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2337\/diaspect.17.4.225","article-title":"Erectile dysfunction in diabetic patients","volume":"17","author":"Penson","year":"2004","journal-title":"Diabetes Spectrum"},{"key":"2023012309520145800_bib20","first-page":"1","article-title":"Phoneutria nigriventer venom and toxins: A review","volume":"Vol. I. Chapt 4","author":"De Lima","year":"2015","journal-title":"Spider venoms"},{"key":"2023012309520145800_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5534\/wjmh.2016.34.1.1","article-title":"Clinical management of priapism: A review","volume":"34","author":"Shigehara","year":"2016","journal-title":"World J Mens Health"},{"key":"2023012309520145800_bib22","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.toxicon.2008.02.010","article-title":"Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function","volume":"51","author":"Nunes","year":"2008","journal-title":"Toxicon"},{"key":"2023012309520145800_bib23","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.toxicon.2012.06.006","article-title":"Phoneutria nigriventer spider toxin Tx2-6 causes priapism and death: A histopathological investigation in mice","volume":"60","author":"Leite","year":"2012","journal-title":"Toxicon"},{"key":"2023012309520145800_bib24","first-page":"1481","article-title":"PnPP-19, a synthetic and nontoxic peptide designed from a Phoneutria nigriventer toxin, potentiates erectile function via NO\/cGMP","volume":"194","author":"Silva","year":"2015","journal-title":"J\u00a0Urol"},{"key":"2023012309520145800_bib25","doi-asserted-by":"publisher","DOI":"10.3791\/56798","article-title":"Intracavernosal pressure recording to evaluate erectile function in rodents","volume":"136","author":"Zhang","year":"2018","journal-title":"J\u00a0Vis Exp"},{"key":"2023012309520145800_bib26","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/0003-2697(77)90192-0","article-title":"Radioiodination of scorpion and snake toxins","volume":"82","author":"Rochat","year":"1977","journal-title":"Anal Biochem"},{"key":"2023012309520145800_bib27","doi-asserted-by":"crossref","first-page":"908","DOI":"10.4330\/wjc.v6.i9.908","article-title":"Management of erectile dysfunction in hypertension: Tips and tricks","volume":"6","author":"Viigimaa","year":"2014","journal-title":"World J Cardiol"},{"key":"2023012309520145800_bib28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0090-4295(02)02102-7","article-title":"Epidemiology of erectile dysfunction in four countries: Cross-national study of the prevalence and correlates of erectile dysfunction","volume":"61","author":"Nicolosi","year":"2003","journal-title":"Urology"},{"key":"2023012309520145800_bib29","doi-asserted-by":"crossref","first-page":"R682","DOI":"10.1152\/ajpregu.00349.2002","article-title":"Erectile dysfunction in spontaneously hypertensive rats: Pathophysiological mechanisms","volume":"284","author":"Behr-Roussel","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2023012309520145800_bib30","first-page":"95","article-title":"Diabetes and sexual dysfunction: Current perspectives","volume":"7","author":"Maiorino","year":"2014","journal-title":"Diabetes Metab Syndr Obes"},{"key":"2023012309520145800_bib31","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.2337\/diacare.25.8.1458","article-title":"Association of type and duration of diabetes with erectile dysfunction in a large cohort of men","volume":"25","author":"Bacon","year":"2002","journal-title":"Diabetes Care"},{"key":"2023012309520145800_bib32","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1517\/14728214.2015.1021682","article-title":"Emerging drugs for the treatment of erectile dysfunction","volume":"20","author":"Peak","year":"2015","journal-title":"Expert Opin Emerg Drugs"},{"key":"2023012309520145800_bib33","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.2165\/00003495-200565120-00003","article-title":"A\u00a0comparative review of the options for treatment of erectile dysfunction: Which treatment for which patient?","volume":"65","author":"Hatzimouratidis","year":"2005","journal-title":"Drugs"},{"key":"2023012309520145800_bib34","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1046\/j.0306-5251.2001.00027.x","article-title":"Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: Absolute bioavailability, food effects and dose proportionality","volume":"53","author":"Nichols","year":"2002","journal-title":"Br J Clin Pharmacol"},{"key":"2023012309520145800_bib35","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1161\/01.CIR.102.20.2516","article-title":"Effects of sildenafil citrate (Viagra) combined with nitrate on the heart","volume":"102","author":"Ishikura","year":"2000","journal-title":"Circulation"},{"key":"2023012309520145800_bib36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jconrel.2009.10.016","article-title":"Nanotechnology and the transdermal route: A state of the art review and critical appraisal","volume":"141","author":"Cevec","year":"2010","journal-title":"J\u00a0Control Release"},{"key":"2023012309520145800_bib37","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.2174\/1567201815666180108170206","article-title":"Physicochemical characterization and skin permeation of cationic transferosomes containing the synthetic peptide PnPP-19","volume":"15","author":"De Marco","year":"2018","journal-title":"Curr Drug Deliv"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519300050?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519300050?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/16\/3\/365\/48589639\/jsm_16_3_365.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/16\/3\/365\/48589639\/jsm_16_3_365.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T10:30:11Z","timestamp":1674469811000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/16\/3\/365\/6980734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,14]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2,14]]},"published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.01.004","relation":{},"ISSN":["1743-6109","1743-6095"],"issn-type":[{"value":"1743-6109","type":"electronic"},{"value":"1743-6095","type":"print"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,2,14]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration","name":"articletitle","label":"Article Title"},{"value":"The Journal of Sexual Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.01.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}