Reserpine (Depressing antihypertension medication)

An aromatic ring, two carbons, and a nitrogen will get you a lot of places.From hallucinogens to decongestants to speed, the arylethylamine moiety works because it tickles neurotransmitter receptors. The effects of the assorted monoamine neurotransmitters are as varied as those of the drugs that mimic it - hypertensive, euphoriant, the works. This is part of how we try to explain to ourselves how antidepressants that block the breakdown of these neurotransmitters (MAO inhibitors) or their reuptake (SSRIs) might be working. What might happen if you took something that depleted some of those monoamine neurotransmitters?

Interestingly, we tried just that for awhile in the 1950's. Reserpine throws a wrench into monoamine metabolism, resulting in lowered blood pressure - which is what doctors were after. Unfortunately, as you might expect, it's a sort of anti-Prozac. Depleting monoamines worked a treat in lowering blood pressure, but some reported that it caused depression. This was actually where the "monoamine hypothesis" was forged - it seemed to fit, deplete monoamines, get depressed. That MAOIs were antidepressants fit nicely. However, things aren't so simple - that reserpine causes depression is now questioned, but we know agents that work on monoamines seem to be working. When papers like the above are published, you know you don't have a very good model. Trouble is, nobody's done much better.