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Nicotinoyl-Tryptamine Derivatives as Potential Dual-Action Prodrugs for NAD⁺ Enhancement and Neuroprotection

A novel class of hybrid molecules is described in which nicotinic acid (vitamin B3) is covalently conjugated to substituted tryptamine scaffolds via an amide bond. Twelve compounds are presented in total; eleven represent new chemical entities. The series encompasses 4-hydroxy-, 5-methoxy-, 4-acetoxy-, 4-phosphoryloxy-, and N-alkyl-substituted variants, including a direct nicotinoyl conjugate of psilocin (4-HO-DMT). These molecules are proposed as potential dual-action prodrugs: enzymatic hydrolysis of the amide bond in vivo would liberate free nicotinic acid - a NAD⁺ precursor active in the Preiss-Handler pathway - alongside pharmacologically active hydroxytryptamine derivatives capable of serotonergic receptor modulation. No synthesis or biological testing has been performed; this preprint presents the structural framework to stimulate further investigation.

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Journal
Zenodo (CERN European Organization for Nuclear Research)
Date
2026-02-28
Source
OpenAlex
DOI
10.5281/zenodo.18825289
PubMed
Unavailable

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