White powders marketed on grocery shelves as “bath salts” are quickly becoming problematic for politicians and police, as reported in the July 17th New York Times. These “salts,” derivatives of a compound called methylenedioxypyrovalerone (MDPV) cause many of the same symptoms as methamphetamine intoxication. The wide availability of these new mixtures, compounded by their ease of synthesis and seemingly no lack of supply, has led to an explosion in their abuse (Note: I won’t cover the chemistry behind MDPV, the active ingredient, because my in silico mentor David Kroll’s posts on Terra Sigilata have mostly covered it).
That’s the gist of the article, in which illicit chemical synthesis fuels a new drug craze, and the public perception of chemists is dragged down again by sound bites such as “state bans thwarted by chemists who have to change only one molecule… to make [the salts] legal.” What happened to fair and balanced coverage?
For every illegal manufacturer of psychoactive compounds hoping for addiction to promote sales, there are many more chemists working on analogs of bioactive substances to treat disease. Compounds that show high potential for abuse tend to interact with three neurotransmitters: serotonin, dopamine, and norepinephrine. In the case of bath salts, the main ingredient is a norepinephrine-dopamine reuptake inhibitor (NDRI), which allows these neurotransmitters to stay longer in the synapse, creating feelings of pleasure and wakefulness. Phenethylamines, such as MDPV, meth, or Ecstasy, the popular club drug, are one major class of compounds which activates these receptors, and are easily tweaked synthetically to prepare drug leads for Parkinson’s disease, schizophrenia, and ADHD.
|Photo Credit: obrag.org|
Janda (JACS 2011, 6587) attaches a six-carbon chain ending in a thiol (SH) group to the amino group of (+)-methamphetamine, the more potent enantiomer, and observes high antibody titres in mouse models. Carroll (J Med Chem, 2011, ASAP) also uses a sulfur antigen, but attaches his via an amide linker connected to the aromatic core. After connecting this linker to a suitable immune-responsive protein, Carroll generates a monoclonal antibody with a 6.8 nm KD for (+)-meth.