Nicotinoyl-Tryptamine Derivatives as Potential Dual-Action Prodrugs for NAD⁺ Enhancement and Neuroprotection
Zenodo (CERN European Organization for Nuclear Research) March 1, 2026 Peer reviewed DOI: 10.5281/zenodo.18825289 via OpenAlex
Summary
A new class of hybrid molecules has been developed that combines nicotinic acid with substituted tryptamine scaffolds through an amide bond. This includes eleven new chemical entities, such as variants with different substitutions and a direct conjugate of psilocin. These compounds are proposed as potential prodrugs that could release nicotinic acid and active hydroxytryptamine derivatives in vivo. However, no synthesis or biological testing has yet been conducted.
Study at a glance
| Design | preprint |
|---|---|
| Key finding | The study presents a novel series of hybrid molecules that may act as dual-action prodrugs, but no experimental testing has been performed. |
Abstract
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.