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• W2080760021 endingPage "4144" @default.
• W2080760021 startingPage "4135" @default.
• W2080760021 abstract "Synthetic hallucinogenic tryptamines, especially those originally described by Alexander Shulgin, continue to be abused in the USA. The range of subjective experiences produced by different tryptamines suggests that multiple neurochemical mechanisms are involved in their actions, in addition to the established role of agonist activity at serotonin 2A (5-HT₂A) receptors.This study evaluated the interaction of a series of synthetic tryptamines with biogenic amine neurotransmitter transporters and with serotonin (5-HT) receptor subtypes implicated in psychedelic effects.Neurotransmitter transporter activity was determined in rat brain synaptosomes. Receptor activity was determined using calcium mobilization and DiscoveRx PathHunter assays in HEK293, Gα16-CHO, and CHOk1 cells transfected with human receptors.Twenty-one tryptamines were analyzed in transporter uptake and release assays, and 5-HT₂A, serotonin 1A (5-HT₁A), and 5-HT₂A β-arrestin functional assays. Eight of the compounds were found to have 5-HT-releasing activity. Thirteen compounds were found to be 5-HT uptake inhibitors or were inactive. All tryptamines were 5-HT₂A agonists with a range of potencies and efficacies, but only a few compounds were 5-HT1A agonists. Most tryptamines recruited β-arrestin through 5-HT₂A activation.All psychoactive tryptamines are 5-HT₂A agonists, but 5-HT transporter (SERT) activity may contribute significantly to the pharmacology of certain compounds. The in vitro transporter data confirm structure-activity trends for releasers and uptake inhibitors whereby releasers tend to be structurally smaller compounds. Interestingly, two tertiary amines were found to be selective substrates at SERT, which dispels the notion that 5-HT-releasing activity is limited only to primary or secondary amines." @default.
• W2080760021 created "2016-06-24" @default.
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• W2080760021 date "2014-05-07" @default.
• W2080760021 modified "2023-10-16" @default.
• W2080760021 title "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes" @default.
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• W2080760021 doi "https://doi.org/10.1007/s00213-014-3557-7" @default.
• W2080760021 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4194234" @default.
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