Nicotinoyl-Tryptamine Derivatives as Potential Dual-Action Prodrugs for NAD⁺ Enhancement and Neuroprotection
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.
Fields of Study & Subjects
Psychedelics and Drug Studies
Alkaloids: synthesis and pharmacology
Sirtuins and Resveratrol in Medicine
Publication details
- Journal / source
- Zenodo (CERN European Organization for Nuclear Research)
- Publication date
- 1 March 2026
- Language
- EN