The Hive > Novel Discourse
Nicodem:
Possible implication of myristicin as a psychotropic substance
Alexander T. Shulgin
Nature 210, 380-284 (1966).
comment: A lot of info on myristicin and similar compounds as well as some hypotheses on the biotransformation and theoretical modes of its psychotropic action. Off course, most hypotheses were later found erroneous but it is still a good read for non-chemists also.
Rhodium:
Centrally Active N-Substituted Analogs of 3,4-Methylenedioxyphenylisopropylamine (3,4-Methylenedioxyamphetamine)
Ulrich Braun, Alexander T. Shulgin and Gisela Braun
J. Pharm. Sci. 69(2), 192-195 (1980) (https://www.thevespiary.org/rhodium/Rhodium/pdf/shulgin/shulgin.n-alkyl-mda.pdf)
Abstract
The known central nervous system activity of 3,4-methylenedioxyphenylisopropylamine and its N-methyl homolog prompted the synthesis of a series of analogs with substituents on the nitrogen atom. Most of these analogs (R = alkyl, alkenyl, hydroxy, alkoxy, and alkoxyalkyl) were prepared by the reductive alkylation of 3,4-methylenedioxyphenylacetone with the appropriate amine and sodium cyanoborohydride. Hindered isomers were synthesized indirectly. Measurements of their pharmacological activity in several animal assays and in human subjects indicated that the central activity decreased with the increased bulk of the N-substituent.
This article has been mentioned before in the following posts:
Post 54080 (Sonson: "High-yielding synthesis of MDA from MDP2P", Methods Discourse)
Post 351891 (bbell: "synthesis xtc", Methods Discourse)
Rhodium:
Molecular Connectivity Analysis of Hallucinogenic Mescaline Analogs
R. A. Glennon, L. B. Kier, and A. T. Shulgin
Journal of Pharmaceutical Sciences, Vol. 68, No. 7, 906-907 (1979) (https://www.thevespiary.org/rhodium/Rhodium/pdf/shulgin/shulgin.molecular.connectivity.pdf)
Abstract
The hallucinogenic (psychotomimetic) potency of 10 mescaline analogs was examined by molecular connectivity analysis. Potencies could be described by a two-term relating equation. which explained 94% of the variance in activity. on the basis of structural variation. 2,5-Dimethoxy substitution as well as the nature of the 4-position substituent played an important role in determining hallucinogenic potency. With the relating equation, reasonable potency predictions were made for six compounds not included in the initial investigation.
Lego:
Application of Ligand SAR, Receptor Modeling and Receptor Mutagenesis to the Discovery and Development of a New class of 5-HT2A Ligands
R.B. Westkaemper, R.A. Glennon
Curr. Top. Med. Chem., 2002, 2(6), 575-598
No DOI found
Abstract
The present review describes our approach to the development of a structurally unique class of 5- HT2A ligands. On the basis of an abbreviated graphics model of a 5-HT2A serotonin receptor, it was hypothesized that introduction of an additional aromatic ring might enhance the affinity of phenylethylamine (an agent that lacks significant affinity for the 5-HT2A receptors). Continued work with such structures, and the continual refinement of graphics receptor models, ultimately led to the identification of AMDA (27, 5-HT2A Ki = 20 nM). AMDA is a 5-HT2A antagonist that, unlike certain other tricyclic 5-HT2A antagonists, binds with very low affinity at dopamine D2 receptors, the serotonin transporter, and the norepinephrine transporter. Comparative structure-affinity studies indicate that AMDA binds in a manner distinct from the tricyclic antagonists Graphics models were employed to identify possible modes of binding. This investigation illustrates the impact of a combination of classical medicinal chemistry, receptor modeling, and molecular biology on novel drug design.
This is a must read for every bee interested in the molecular action of hallucinogens. This article provides an insight in the structural differences between agonists and antagonists at the 5-HT2A rececptor.
Lego really enjoyed this article!
Ganesha:
Great review. I'm a bit sceptical about AMDA. This promising affinity dosen't meen that there is magic to be found in AMDA type of componds. For instance, 4-(n)hexyl-2,5-dimethoxy-AMPH has 16,4 times more 5-HT2A affinity than DOB, but considering the character of DOAM, the 4-(n)hexyl would most likely be pretty uninteresting. Let's hope AMDA will show interesting activity...
Navigation
[0] Message Index
[#] Next page
[*] Previous page
Go to full version