Linked Life Data

19756361

Source:http://linkedlifedata.com/resource/pubmed/id/19756361

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-1-21
pubmed:abstractText
N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N-methyl-N-isopropyltryptamine (MIPT), N,N-dipropyltryptamine (DPT), and N,N-diisopropyltryptamine. We then tested the abilities of these N,N-dialkyltryptamines to inhibit [(3)H]5-HT uptake via the plasma membrane serotonin transporter (SERT) in human platelets and via the vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The tryptamines were also tested as inhibitors of [(3)H]paroxetine binding to the SERT and [(3)H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT, MIPT, DPT, and DIPT inhibit [(3)H]5-HT transport at the SERT with K ( I ) values of 4.00 +/- 0.70, 8.88 +/- 4.7, 0.594 +/- 0.12, and 2.32 +/- 0.46 microM, respectively. At VMAT2, the tryptamines inhibited [(3)H]5-HT transport with K ( I ) values of 93 +/- 6.8, 20 +/- 4.3, 19 +/- 2.3, and 19 +/- 3.1 muM, respectively. On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Hallucinogens, http://linkedlifedata.com/resource/pubmed/chemical/N,N-Dimethyltryptamine, http://linkedlifedata.com/resource/pubmed/chemical/N,N-diisopropyltryptamine, http://linkedlifedata.com/resource/pubmed/chemical/Paroxetine, http://linkedlifedata.com/resource/pubmed/chemical/SLC6A4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane..., http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Slc18a2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Tetrabenazine, http://linkedlifedata.com/resource/pubmed/chemical/Tritium, http://linkedlifedata.com/resource/pubmed/chemical/Tryptamines, http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Monoamine Transport..., http://linkedlifedata.com/resource/pubmed/chemical/dihydrotetrabenazine, http://linkedlifedata.com/resource/pubmed/chemical/dipropyltryptamine
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1435-1463
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1591-9
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.
pubmed:affiliation
Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Wisconsin, WI 53706, USA. cozzi@wisc.edu
pubmed:publicationType
Journal Article