{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:54:29Z","timestamp":1791644069285,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,7,12]],"date-time":"2013-07-12T00:00:00Z","timestamp":1373587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,8]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Oxytocin (\n OT<\/jats:styled-content>\n ) plays a major role in the control of male sexual responses. Notably, blockade of\n OT<\/jats:styled-content>\n receptors has been reported to inhibit ejaculation in animals. The study aimed to investigate the action of a highly selective, non\u2010peptide\n OT<\/jats:styled-content>\n antagonist\n GSK<\/jats:styled-content>\n 557296 in a model of pharmacologically induced ejaculation in anaesthetized rats. The site of action was assessed by investigating different delivery routes for this compound.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Urethane\u2010anaesthetized\n W<\/jats:styled-content>\n istar rats were implanted with a cerebral ventricle cannula for i.c.v. injections or with a subdural catheter for intrathecal (i.t.)\n GSK<\/jats:styled-content>\n 557296 injections. Occurrence of ejaculation was assessed following i.v. 7\u2010hydroxy\u20102\u2010(di\u2010\n N<\/jats:styled-content>\n \u2010propylamino)tetralin (7\u2010\n OH<\/jats:styled-content>\n \u2010DPAT<\/jats:styled-content>\n ), a dopamine\n D3<\/jats:styled-content>\n receptor agonist. In addition, seminal vesicle pressures (\n SVP<\/jats:styled-content>\n ) and bulbospongiosus muscle (\n BS<\/jats:styled-content>\n )\n EMG<\/jats:styled-content>\n were recorded as physiological markers of emission and expulsion phases of ejaculation respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Highest i.v.\n GSK<\/jats:styled-content>\n 557296 dose reduced occurrence of ejaculation and increases in\n SVP<\/jats:styled-content>\n but had no effect on\n BS<\/jats:styled-content>\n \u2010\n EMG<\/jats:styled-content>\n . I.c.v.\n GSK<\/jats:styled-content>\n 557296 dose dependently inhibited ejaculation, increases in\n SVP<\/jats:styled-content>\n and\n BS<\/jats:styled-content>\n contractions. At spinal thoracic level,\n GSK<\/jats:styled-content>\n 557296 dose dependently inhibited ejaculation and increases in\n SVP<\/jats:styled-content>\n but\n BS<\/jats:styled-content>\n \u2010\n EMG<\/jats:styled-content>\n was impaired only with the highest dose. When delivered at lumbar level,\n GSK<\/jats:styled-content>\n 557296 dose dependently inhibited ejaculation, increases in\n SVP<\/jats:styled-content>\n and\n BS<\/jats:styled-content>\n contractions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n In the 7\u2010\n OH<\/jats:styled-content>\n \u2010DPAT<\/jats:styled-content>\n \u2010induced ejaculation model,\n GSK<\/jats:styled-content>\n 557296 acts peripherally and centrally to inhibit ejaculation with different modalities. Blockade of brain\n OT<\/jats:styled-content>\n receptors seems to be the most effective mechanism of action. Targeting central\n OT<\/jats:styled-content>\n receptors with highly selective antagonist seems a promising approach for the treatment of premature ejaculation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12198","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T07:13:27Z","timestamp":1364368407000},"page":"1477-1485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Inhibition of ejaculation by the non\u2010peptide oxytocin receptor antagonist\n GSK<\/scp>\n 557296: a multi\u2010level site of action"],"prefix":"10.1111","volume":"169","author":[{"given":"Pierre","family":"Cl\u00e9ment","sequence":"first","affiliation":[{"name":"Pelvipharm Laboratories Orsay France"},{"name":"SIRIUS\u2010EA4501 University of Versailles\u2010Saint Quentin en Yvelines Montigny le Bretonneux 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