Show simple item record

dc.contributor.authorPardo-Lozano, Ricardo
dc.contributor.authorFarré, Magí
dc.contributor.authorYubero-Lahoz, Samanta
dc.contributor.authorO’Mathúna, Brian
dc.contributor.authorTorrens, M.
dc.contributor.authorMustata, Cristina
dc.contributor.authorPérez-Mañá, Clara
dc.contributor.authorLangohr, Klaus
dc.contributor.authorCuyàs, Elisabet
dc.contributor.authorCarbó, Marcel·lí
dc.contributor.authorde la Torre, Rafael
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa
dc.date.accessioned2012-12-11T08:38:47Z
dc.date.available2012-12-11T08:38:47Z
dc.date.created2012-10-24
dc.date.issued2012-10-24
dc.identifier.citationPardo-Lozano, R. [et al.]. Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy''): the influence of gender and genetics (CYP2D6, COMT, 5-HTT). "PLoS One", 24 Octubre 2012, vol. 7, núm. 10, p. 1-10.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/2117/17091
dc.description.abstractThe synthetic psychostimulant MDMA (63,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75–100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role.
dc.format.extent10 p.
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
dc.subject.lcshBiomathematics
dc.titleClinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy''): the influence of gender and genetics (CYP2D6, COMT, 5-HTT)
dc.typeArticle
dc.subject.lemacBiomatemàtica
dc.contributor.groupUniversitat Politècnica de Catalunya. GREMA - Grup de Recerca en Estadística Matemàtica i les seves Aplicacions
dc.identifier.doi10.1371/journal.pone.0047599
dc.description.peerreviewedPeer Reviewed
dc.subject.ams92B Mathematical biology in general
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047599
dc.rights.accessOpen Access
drac.iddocument11021617
dc.description.versionPostprint (published version)
upcommons.citation.authorPardo-Lozano, R.; Farré, M.; Yubero-Lahoz, S.; O’Mathúna, B.; Torrens, M.; Mustata, C.; Pérez-Mañá, C.; Langohr, K.; Cuyàs, E.; Carbó, M.; de la Torre, R.
upcommons.citation.publishedtrue
upcommons.citation.publicationNamePLoS One
upcommons.citation.volume7
upcommons.citation.number10
upcommons.citation.startingPage1
upcommons.citation.endingPage10
dc.identifier.pmid23112822


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Except where otherwise noted, content on this work is licensed under a Creative Commons license: Attribution-NonCommercial-NoDerivs 3.0 Spain