{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:32:13Z","timestamp":1778599933144,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"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":[[2014,1]]},"abstract":"Background and Purpose<\/jats:title>The cardiovascular effects produced by 3,4\u2010methylenedioxymethamphetamine (MDMA<\/jats:styled-content>; \u2018E<\/jats:styled-content>cstasy\u2019) contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA<\/jats:styled-content> metabolites on cardiovascular function in rats.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA<\/jats:styled-content> and its phase I<\/jats:styled-content> metabolites on BP<\/jats:styled-content>, heart rate (HR<\/jats:styled-content>) and locomotor activity in conscious male rats.<\/jats:p><\/jats:sec>Key Results<\/jats:title>MDMA<\/jats:styled-content> (1\u201320\u2009mg\u00b7kg\u22121<\/jats:sup>) produced dose\u2010related increases in BP<\/jats:styled-content>, HR<\/jats:styled-content> and activity. The peak effects on HR<\/jats:styled-content> occurred at a lower dose than peak effects on BP<\/jats:styled-content> or activity. The N<\/jats:styled-content><\/jats:italic>\u2010demethylated metabolite, 3,4\u2010methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA<\/jats:styled-content>. The metabolite 3,4\u2010dihydroxymethamphetamine (HHMA<\/jats:styled-content>; 1\u201310\u2009mg\u00b7kg\u22121<\/jats:sup>) increased HR<\/jats:styled-content> more potently and to a greater extent than MDMA<\/jats:styled-content>, whereas 3,4\u2010dihydroxyamphetamine (HHA) increased HR<\/jats:styled-content>, but to a lesser extent than HHMA<\/jats:styled-content>. Neither dihydroxy metabolite altered motor activity. The metabolites 4\u2010hydroxy\u20103\u2010methoxymethamphetamine (HMMA) and 4\u2010hydroxy\u20103\u2010methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA<\/jats:styled-content> and HHMA<\/jats:styled-content> was blocked by the \u03b2<\/jats:styled-content>\u2010adrenoceptor antagonist propranolol.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>Our results demonstrate that HHMA<\/jats:styled-content> may contribute significantly to the cardiovascular effects of MDMA<\/jats:styled-content>\u2005in vivo<\/jats:italic>. As such, determining the molecular mechanism of action of HHMA<\/jats:styled-content> and the other hydroxyl metabolites of MDMA<\/jats:styled-content> warrants further study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12423","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:03:36Z","timestamp":1381539816000},"page":"83-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Effects of 3,4\u2010methylenedioxymethamphetamine (MDMA<\/scp>) and its main metabolites on cardiovascular function in conscious rats"],"prefix":"10.1111","volume":"171","author":[{"given":"Charles W","family":"Schindler","sequence":"first","affiliation":[{"name":"Preclinical Pharmacology National Institutes of Health National Institute on Drug Abuse Intramural Research Program Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric 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