The hallucinogenic phenylalkylamine (4-bromo-2,5-dimethoxyphenyl)-2-aminoethane (2C-B) is displayed in the upper image, tilted slightly out-of-plane, in an energy-minimized conformation with its van der Waals surface superimposed. The van der Waals surface comprises the set of points of maximal attraction between two neutral molecules due to
The lower image shows 2C-B with a hydrophobic potential overlay. Brown represents the most hydrophobic region, green is intermediate, and blue represents the least hydrophobic region. Thus, the bromine atom is the most lipid-soluble part of the 2C-B molecule and the amine nitrogen is the most water-soluble. These properties influence where and how tightly a molecule will bind to a receptor. For 2C-B binding to the 5-HT2 receptor family, the implication is that these receptors may contain valines, leucines, or isoleucines in the region that interacts with the bromine atom. The hydrophilic amine nitrogen, on the other hand, most likely interacts with a charged, water-soluble residue such as aspartate or glutamate.
2C-B is a selective partial agonist ligand for the serotonin 5-HT2A and 5-HT2C receptors, members of a large family of G-protein coupled receptors that regulate intracellular calcium levels. These serotonin receptors are found throughout the brain, but 5-HT2A receptors are most densely populated in layer IV of the cerebral cortex, while 5-HT2C receptors are found mainly in the choroid plexus. The action of 2C-B at the serotonin receptors suggests a role for these receptors in sensory information processing and other cognitive functions.
These images were generated on a Silicon Graphics O2 workstation using the molecular modeling program Sybyl. The energy minimization was computed by the Powell method using energy steps of 0.01 kcal/mol with 10,000 iterations.