Pharyngula: Mulifunction drugs.

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Mulifunction drugs.

Category:
Posted on: October 29, 2007 4:04 PM, by harderkid13

While I would love to devote all of my time to neurobiology, I do have other classes that require my attention. In one of those classes I am writing a research paper on tuberculosis. While researching tuberculosis I began wondering if there were any strange cases where tuberculosis has neurobiological effects. A google search brought me to this article. While this is not exactly what I was looking for, it did pique my interest. It seems like drugs taken for one thing end up treating another as well. In Biochemistry we recently had to read an article about how the obesity drug Orlistat is a possible cancer treatment. I just wonder how people first begin to realize that a drug taken for one thing affects other areas as well.

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Viagra started out as a heart medicine. In trials, men started getting erections, and the rest is pharmaceutical history.

Posted by: H. Humbert | October 29, 2007 4:30 PM

My wife takes Methotrexate for her arthritis. Its original and still prevalent use is for cancer treatment, but many women who had both cancer and arthritis found that it treated both. For my wife, it has been a miracle drug taking her from near immobility to skiing, windsurfing, swimming a mile every day, and other activities. Given that most natural biological molecules have multiple uses in the critters that make them, and even different uses in different critters, and that many biological functions can be performed by different molecules, giving a high level of redundancy and plasticity, perhaps you discovery should not be at all surprising.

Posted by: AnInGe | October 29, 2007 4:42 PM

I take PCP because it's fun, but I've also noticed that it makes me impervious to bullets.

Posted by: Gordon S | October 29, 2007 4:42 PM

The monoamine oxidase inhibitors, the 1st generation anti-depressants, initially started out as a treatment for tuberculosis as well. Specifically, Iproniazid was being used in the 1950's for TB when it was noted as having a mood-lightening effect.

Also, Zyban, the smoking cessation drug, was noted as reducing smoking while being evaluated as an anti-depressant (marketed for this purpose under the name Wellbutrin; buproprion is the drug name). There are a host of other drugs with similar histories.

Posted by: Bryan | October 29, 2007 4:44 PM

In fact that's one of the strategies for innovation (read "desperation when other avenues start failing"). An antidepressant showed diuretic properties and was turned into a b.p. lowering drug among other examples.

Posted by: Ashutosh | October 29, 2007 4:48 PM

Thalidomide was a treatment for morning sickness, but cured lots of people of masturbation.

Oh. That's awful. Pretend you didn't read that and move along.

Posted by: Frac | October 29, 2007 4:49 PM

This should not be surprising to you. Think about it for a moment. You have heard of side effects, no? Many of them are undesirable, others merely an inconvenience, and some are even beneficial. This is nothing more than a drug or its metabolites interacting with different "targets" than was initially intended.

Posted by: shiftlessbum | October 29, 2007 4:50 PM

"I just wonder how people first begin to realize that a drug taken for one thing affects other areas as well."
One way is certainly observation; people notice that some group of people either exhibit or don't exhibit certain symptoms. For example it is general belief (and as far as I know may be true) that bee keepers rarely get arthritis or MS. So treatments for these probelms have been tried by using bee stings. (With very mixed results.).
A treatment not used much any more is shock treatment - one form of this insulin shock came about his way:
"Sakel discovered accidentally, by causing convulsions with an overdose of insulin, that the treatment was efficient with patients afflicted with psychosis, particularly schizophrenia. "
So often times it was jut playing with or trying to fix one thing ad noticing another effect. On the other hand looking at thepaper you presented it seemed that maybe when they saw the effect he drug had on NMDA, the figured -"ah now that might work..."

Posted by: sailor | October 29, 2007 4:51 PM

Thalidomide was a treatment for morning sickness, but cured lots of people of masturbation.

Well, that WAS awful, but thalidomide is an effective therapy for Hansen's disease (leprosy) and certain kinds of leukemias.

Posted by: shiftlessbum | October 29, 2007 4:52 PM

#10

I tend to look at drugs as the biological equivalent of the "Game Genie", a gadget you plugged into your Super Nintendo (between the console and your game cartridge) which allowed you to get extra lives, and unlock nifty features by modifying key spots in the cartridge's program code. Anyone who experimented with POKEs on a Commodore64 or TRS-80 ColorComputer know what I mean, too. (Have I dated myself yet?)

It was largely hit-and-miss, but you can make some cool things happen, or fix things that didn't work the way they should've. However, most of the results and their side effects could be unpredictable, even if you knew what you were doing.

Anyone get what I'm saying here? It's just something I've had in my head for years, and I finally got a chance to say it.

Posted by: Anonymous Prime | October 29, 2007 4:55 PM

#11

Thalidomide is a tumor necrosis factor inhibitor. Meningeal TB is relatively common in children between the ages of 4 months and 4 years old and can result in disorientation, abnormal movements and speech abnormalities. See Udani, PM et al. 1971. J. Neurol. Sci. 14:341-357. For a more recent review see Yaramis, A. 1998. Pediatrics 102. Also, Jaffe, IP 1982. Lancet 1:738.

Posted by: pdiddysl | October 29, 2007 5:01 PM

#12

There are numerous examples of this. A fun one is minoxidil, which was first invented as a treatment for hypertension - and in pill form it is remarkably good at that. However in topical form it is known a Rogaine and has been found to cause hair growth/hair retention in balding men. The pill also has a hair-growth side-effect, but it is unfortunately not specific to the head.

All of these examples are a result of a more fundamental fact of cell biology/physiology, which is that the receptors to which medications bind are seldom found in a single tissue or in a single organ, and are not limited to a single function. Inhibition of cyclooxygenase by aspirin causes analgesia in inflamed tissues but also causes inactivation of aggregation in platelets, leading to unwanted bleeding, or life-preserving clot prevention.

Posted by: Dr. Steve | October 29, 2007 5:09 PM

#13

Of course a drug taken for one thing affects other areas.

You act like this is some great discovery, moron.

Posted by: Randolph | October 29, 2007 5:41 PM

#14

Yeah Randolph, tell it like it is!
Caledonian stumbled and fell on the battlefield but looks like someone already is taking charge of the flag for random boorishness...

Posted by: Arnaud | October 29, 2007 5:52 PM

#15

Riddle: How can anestheisiologists assist psychiatrists? In the 1950s, French anesthesiologists used the class of phenothiazine "major tranquillizers" as an adjunct in anesthesia. They serendipitiously noticed that the symptoms of individuals 'diagnosed' with schizophrenia improved post-anesthesia.

The commonest use of side effects in preference to effects probably involves off-the-shelf antihistamines, which are used as antinauseants, decongestants, and, hypnotics.

Posted by: salient | October 29, 2007 5:57 PM

#16

What I find interesting is how some drugs can affect people who are not even using them.

For instance, alcohol makes me funnier, smarter, and more interesting, while simultaneously making any women near me more attractive.

However, the effects can vary wildly: when my father used alcohol, it would simultaneously make him angry and my mom cry.

Posted by: Brownian, OM | October 29, 2007 6:13 PM

#17

The first thing my pharmacology professor said to us was, "There are no side effects--only effects. Some we like, some we don't."

Posted by: PalMD | October 29, 2007 6:50 PM

#18

Strangely enough I was talking to a chap in the pub last night who copped TB which then caused meningitis. It caused some brain damage - balance, vision problems and memory loss. he is having to relearn things he previously knew, and has had to sell his beloved boat.

He does, however remember the hospital consulting telling my friend he was 'very unlucky' and that in his whole career he had heard of ten such cases but never seen one.

Posted by: Peter McGrath | October 29, 2007 6:54 PM

#19

If acetyl-salicylic acid (aspirin) were up for FDA approval today it might not get it, it is a rather dirty drug. Do you want it for pain relief? or to remove inflammation? how about to thin the blood? beware of the effect on your stomach etc etc.

There are many single gene diseases, knockout mice or mutations that have multiple effects. This is because Nature is a conservative, always reusing old things instead of making up novelties. So genes get turned on in lots of different times, places, tissues, situations, roles etc This means drugs that target in individual protein or pathway will almost inevitably have more than one effect.

Then there is the effect of molecules being a bit non specific, so they bind to more than just their target molecule. Vioxx was supposed to be good because it was extra specific. But when it is the proportion of two things that is important, knocking down just one of them can have bad effects...

Posted by: Peter Ashby | October 29, 2007 7:16 PM

#20

Viagra started out as a heart medicine. In trials, men started getting erections, and the rest is pharmaceutical history.

What did you say? Can you speak a little louder please?? :)

Posted by: Amit | October 29, 2007 7:17 PM

#21

Obviously serendipity and good clinical observations play big roles when it comes to identifying new uses for old drugs. But pharmacuetical companies have noticed that from a cost-benefit perspective, it is much more effcient to get old drugs approved for new uses.

Posted by: Becca | October 29, 2007 7:39 PM

#22

Thalidomide was a treatment for morning sickness, but cured lots of people of masturbation.

Oh my goodness.

Posted by: Epistaxis | October 29, 2007 10:58 PM

#23

This is an excellent line of discussion, possibly topic for a blog post of my own.

Oftentimes in the history of medicine, one finds one treatment being used for one thing and ending up correcting another. Examples include:
1) Statins (HMG CoA-Reductase Inhibitors) that lower cholesterol have broad-ranging effects, including antiinflammatory ones.
2) Buproprion, an anti-depressant marketed under the trade name Wellbutrin, was found to help people stop smoking. The same dose and frequency somehow won approval for a new patent as Zyban.
3) Amitriptyline, an antidepressant, was found to have use in reducing neuropathic pain syndromes.
4) Same goes for Doxepin.
5) A form of tuberculosis that was weakened and intended to inoculate people against the actual disease TB was found to be a useful treatment for bladder cancer.
6) A chemist tries to produce artificial quinine. He ends up producing the first aniline dye. Another chap accidentally drops that dye into a bit of tissue culture, notices that it kills a certain kind of cells more than it killed other ones, and basically invented anti-cancer chemotherapy.

Examples are endless and it's one of the more exciting and fun aspects of science. This all happpens because there are processes at work that underpin all these discoveries. Some we know, some we don't, and some we don't even know that we don't know - until we're giving a medicine to treat a certain disease and we notice something bizarre happening with regularity.

Science rocks because of these kinds of unpredictable advances and developments. But all creationism can do is tell people what they already think they know.

BCH

Posted by: Burt Humburg | October 30, 2007 1:13 AM

#24

Frac - it was more prevention than cure.

Another (although far less interesting than those metntioned above) example is using any of the vast array of drugs which cause mild drowsiness as a weak sedative, e.g. cinnarizine and chlorpheniramine (originally anti-travel sickness and antihistamine respectively)

Posted by: tom p | October 30, 2007 7:49 AM

#25

One patient's unwanted side effect is anothers syncretic benefit.

Posted by: jim a | October 30, 2007 8:01 AM

#26

At last, that intervention for Wookiee visualisation deficiency!

http://www.bloomberg.com/apps/news?pid=washingtonstory&sid=aOI2YHf6XnD8

Posted by: Jamie D | October 31, 2007 9:15 AM

#27

@Frac #6: This has to be the best comment I ever read :-)

Posted by: Roman Kopac | October 31, 2007 1:45 PM

#28