Pharmacological Analogues of Erinacine A, Neurotrophic, Geroprotective and Telomerase-Activating.

Pharmacological Analogues of Erinacine A and Hericenones from Hericium erinaceus: Rational Design of Non-Psychedelic Neurotrophic, Nootropic, Antidepressant, Synaptogenic, Myelinogenic, Geroprotective and Telomerase-Activating Agents Yaroslav Grigorievich Zaitsev ORCID: 0000-0002-0069-2997 Preprint · December 2025 Abstract Erinacine A and psilocybin exhibit partially overlapping pharmacological profiles, but differ significantly in lipophilicity and the type of neuroplasticity induced. The fundamentally similar carvacrol and asarone also demonstrate potential as neurotrophic agents, forming a number of pharmacophore assemblies and pharmacological strategies that have formed the basis of rational drug design. Fast neuroplasticity (psilocybin, ketamine) promotes synaptogenesis but can duplicate pathological connections and increase neural noise. In contrast, slow neuroplasticity—true neurogenesis and myelinogenesis—appears to be beneficial in organic brain damage, depression, Alzheimer&disease, and related conditions. The lipophilic and amphiphilic synthetic terpenes and tryptophols presented in this study are targeted at deep neurotrophic activity, primarily targeting 5-HT1A serotonin receptors, both through penetration into deep brain regions and through their high affinity for 5-HT1A receptors in silico analysis .. The structures exhibit particularly low, low, and high affinity, high lipophilicity, and bioavailability. They also possess significant pharmacological...