Planta Medica
April 1, 2006
Niels Jensen, Jochen Gartz, Hartmut Laatsch
56 citations
The hallucinogenic mushroom Inocybe aeruginascens contains typical Psilocybe alkaloids such as psilocybin. Researchers have now determined the structure of an additional indole derivative, aeruginascin, which is the quaternary ammonium compound N,N,N-trimethyl-4-phosphoryloxytryptamine. Aeruginascin is closely related to the frog skin toxin bufotenidine (5-HTQ), a potent 5-HT3 receptor agonist, and has so far been found exclusively in Inocybe aeruginascens.
Journal of Medicinal Chemistry
July 1, 2003
James J. Chambers, Jason C. Parrish, Niels Jensen et al.
27 citations
Conformationally constrained tetrahydronaphthofurans were designed to study the optimal shape of the 2-aminoethyl moiety in phenethylamine-type serotonin 5-HT(2A) receptor agonists. In vitro assays showed that benzofuran-containing analogues (6a and 6b) had significantly higher affinity for 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors than benzodihydrofuran-containing compounds. The most potent compound, 6b, had K(i) values of 2.6 nM at 5-HT(2A) and 1.1 nM at 5-HT(2C) cloned rat receptors. Despite high affinity, these naphthofuran compounds lacked high intrinsic activity at the 5-HT(2A) receptor in the phosphoinositide hydrolysis assay. Compound 6b failed to substitute for LSD in a rat drug discrimination assay, typical for low intrinsic activity compounds. Conformational constraint produced high-affinity partial agonists, but full receptor activation requirements remain unidentified.
January 1, 2005
Niels Jensen
8 citations
Aeruginascin, a natural product from the hallucinogenic mushroom Inocybe aeruginascens, was isolated and identified as 4-phosphoryloxy-N,N,N-trimethyltryptamine, the quaternary trimethylammonium analog of psilocybin. Synthetic aeruginascin matched the isolated sample in all aspects. The mushroom alkaloids norbaeocystin and baeocystin were also synthesized, and a new synthetic route to 4-hydroxy-tryptamines was explored. A series of tryptamines with diverse N-terminal substituents was synthesized to examine binding to serotonin receptors. Most compounds showed nanomolar binding affinities for 5-HT1A, 5-HT2A, and 5-HT2C receptors. In functional 5-HT2A IP accumulation assays, most acted as antagonists or partial agonists.