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Author Ketsela Albertí, Gabriel |
Abstract During the last decade, a notable change in the illicit drug market has been evidenced by the appearance of a new generation of psychoactive substances. Accessible via the Internet or through companies that sell them as “research chemicals”, new psychoactive substances (NPS) continue to increase rapidly, posing a significant risk to public health. Among these substances, the new tryptamines are one of the most frequent classes that became popular because of the hallucinogenic properties similar to LSD. When one of these NPS falls under legislative control, the drug market produces similar and structurally related ones, creating alternative compounds that are not controlled by international law, but with still unknown chemical, pharmacological and toxicological properties. Despite the lack of information, these compounds are known to interact with various serotonin (5-HT) transporters and receptors. This study focuses on the in vitro and in vivo effects of amino group modification of three 5-MeO-tryptamines substituted by N, N-dialkyl, that is, 5-MeO-DMT, 5-MeO-DET, and 5 - MeO-DiPT. The order of affinity (Ki value) at human 5-HT1A and 5-HT2A receptors (CHO-K1 membrane cells) was 5-MeO-DMT> 5-MeO-DET> 5-MeO-DiPT. In contrast, for human SERT (HEK293 cells), 5-MeO-DiPT showed the highest affinity, followed by 5-MeO-DET and 5-MeO-DMT. Furthermore, the order of inhibition of the potency of 5-HT uptake was consistent with the Ki values for the SERT. In general, 5-MeO tryptamines with bulkier N, N-dialkyl groups have a higher affinity for blocking SERT, while reducing the alkyl chain of the amino group increases affinity for 5-HT1A receptors and 5-HT2A. Furthermore, studies in mice examined whether these substances induce the head-twitch response (HTR), a response mediated by the 5-HT2A receptor that is widely used as a behavioral study of hallucinogenic effects in humans. These experiments have shown that 5-MeO-DMT has the highest efficacy, which is correlated with the highest affinity for the 5-HT1A and 5-HT2A receptors. These findings demonstrate that inactivation of the 5-HT1A receptor increases HTR induced by hallucinogenic administration of 5-MeO-tryptamines, revealing the opposite role played by both receptors. |
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Director Berzosa Rodríguez, Xavier |
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Degree IQS SE - Master’s Degree in Pharmaceutical Chemistry |
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Date 2021-09-15
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