Teh Rejects: Drugs that didn't make the cut

When a drug is first isolated/synthesized and preliminarily investigated by a pharmaceutical company for possible development into a marketable drug, it is often assigned a code number for use by the company. If the drug is then found to be capable of producing a useful pharmacological effect (e.g. reducing blood pressure) without serious toxicity (e.g. liver failure) in animals, it is given a catchier name (like ibuprofen or bacitracin) and evaluated in humans in a series of clinical trials. Should these trials confirm the animal results, and the drug is more effective than currently available drugs that do the same thing (if these drugs are available), and the government is happy with the way things were carried out, a new drug can be brought to market. Hooray!

The majority of drugs that are developed by drug companies never make it to market. A good number of them don't even make it to human trials, and thus are never even granted a nifty moniker. Instead, they retain a boring old drug company code, and are filed away in a company storage room and forgotten. However, sometimes pesky scientists get their hands on these defunct drugs and discover that they possess other interesting effects, which they employ to investigate how the body works. This is the story of those drugs, and why they are so gosh darn groovy.

Very rarely, a particular drug company code is so awesome, that it sticks around even after a 'catchier' name has been assigned and the drug reaches market. RU-486, also known as mifepristone (tradenames include Mifegyne and Mifeprex) is used to terminate pregnancy (within 49 days of gestation) and as an emergency contraceptive. It accomplishes these actions by promoting the breakdown and shedding of the uterine endometrium (the lining of the uterus in which the fetus is implanted early on in a pregnancy) and by preventing ovulation (and thus pregnancy). So not a big winner with the pro-lifers.

Reverses the behavioural effects of ethanol. It stops you from being drunk. It does this horrible, horrible thing by blocking the action of ethanol at GABA receptors in the brain. The worst part is that it can't even be used to treat alcohol poisoning, since it doesn't block the respiratory depression that is usually what kills you if you drink way too much. If that wasn't it enough, it also increases the risk of seizures. So not a big winner with anyone.

BRL 37344, CL 316,243, and SR 58611A
These beauties activate lipolysis (i.e. increase the breakdown of fat) in rats and hamsters, which made the drug companies practically wet themselves when they first stumbled upon them (see: the obesity epidemic in America). However, upon further investigation, they were found not to work in humans, since our fat cells don't appreciably express the particular receptor by which these drugs act.

This is a classic example of a promising new drug gone horribly wrong. It was originally developed as a sedative, but when screened for its ability to cause mutations in bacteria (using the Ames test, a quick way of testing to see if something causes cancer without actually having to expose an animal to it and wait to see what develops), it was found to cause mutations in the presence of light. It's chemical structure is such that it can inadvertently absorb light energy and use it to generate reactive oxygen species, which then cause oxidative damage to DNA, leading to mutations.

- Bousquet-Melou A, Galitzky J, Carpene C, Lafontan M, Berlan M. beta-Adrenergic control of lipolysis in primate white fat cells: a comparative study with nonprimate mammals. Am J Physiol. 1994 Jul;267(1 Pt 2):R115-23.
- Ticku MK, Kulkarni SK. Molecular interactions of ethanol with GABAergic system and potential of RO15-4513 as an ethanol antagonist. Pharmacol Biochem Behav. 1988 Jun;30(2):501-10.
- Will O et al. Oxidative DNA damage and mutations induced by a polar photosensitizer, Ro19-8022. Mutat Res. 1999 Sep 13;435(1):89-101.
- http://en.wikipedia.org/wiki/RU486

6 chemically inspired comments:

C.D. Clements said...

Now the drugs don't work
They just make you worse
But I know I'll see your face again

Renzo said...

I can actually see the anti-drunk pill being a *great* tool in the fight against drunk driving. You get to get drunk *and* drive home safely.

Tessa said...

I've heard some people defend coke as their solution being drunk and needing to drive at the end of the night. Clearly, it's a load of hooey, but they say that yay "sobers" them up enough to drive home.

CND said...

I'd be concerned about a drunk person attempting to properly dose themselves with the stuff. Plus they'd have to wait for it to kick in. But yeah, if it could in any way cut down on drunk driving accidents, I'm all for it.

The coke thing scares the bejeebies out of me. Yeah, I want you driving drunk and in a self-righteous mood.

Anthony said...

On the other hand, driving with an increased risk of seizures doesn't sound too great either...

Anonymous said...

The law in relation to DUI doesn't depend on a clinical definition of drunkenness, but rather a defined blood alcohol level. Many chronic alcohol abusers may well be clinically 'sober' at blood levels significantly in excess of the legal allowance but they are still breaking the law!