title: Alpha-ethyltryptamines as dual dopamine-serotonin releasers.
abstract: The dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter releasing activity and serotonin-2A (5-HT2A) receptor agonist activity of a series of substituted tryptamines are reported. Three compounds, 7b, (+)-7d and 7f, were found to be potent dual DA/5-HT releasers and were >10-fold less potent as NE releasers. Additionally, these compounds had different activity profiles at the 5-HT2A receptor. The unique combination of dual DA/5-HT releasing activity and 5-HT2A receptor activity suggests that these compounds could represent a new class of neurotransmitter releasers with therapeutic potential.
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA. Electronic address: beb@rti.org.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Landavazo
authors.affiliation: Medicinal Chemistry Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Partilla
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Decker
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Page
authors.affiliation: Medicinal Chemistry Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Baumann
authors.affiliation: Medicinal Chemistry Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rothman
mesh_terms: D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D009638:Norepinephrine / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D014363:Tryptamines; D012701:Serotonin; C038034:etryptamine; D004298:Dopamine; D009638:Norepinephrine
keywords: 5-HT 2A receptor; 5-HT releasers; DA releasers; Tryptamines