Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.
J Neural Transm (Vienna) September 12, 2009 Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al. 144 citations
N,N-dimethyltryptamine (DMT) and related tryptamines inhibit serotonin transport at the serotonin transporter (SERT) and vesicle monoamine transporter (VMAT2) with varying potencies. DMT, MIPT, DPT, and DIPT inhibited serotonin uptake at SERT with Ki values of 4.00, 8.88, 0.594, and 2.32 µM, respectively. At VMAT2, inhibition was weaker, with Ki values of 93, 20, 19, and 19 µM. The tryptamines were poor inhibitors of radioligand binding to these transporters, yielding high binding-to-uptake ratios. This pattern suggests the tryptamines act as transporter substrates rather than uptake blockers, indicating separate substrate and inhibitor binding sites. The transporters may concentrate tryptamines inside neurons for sigma-1 receptor activation and potential release as transmitters.