Example: Atomoxetine is believed to increase norepinephrine in the brain, to treat ADHD. What do you mean, believed? Then how was it successfully developed to do that in the first place, if the mechanisms of action to effect that change are not known?
Apparently this is not uncommon in medication. How is this possible?
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Main goal is to have medication that works. Understanding how it works is nice, but not necessary. All we need to know are the side effects, and how common they are, as well as interactions with other drugs. Another useful bit of info is minimal dose that still treats the condition (since lower dose mean less side effects).
All of this info can be collected through experiments.
There is a lot of trial and error in the process, but benefits justify the costs.
Understanding how the drug works is useful as it help us find better drugs, ones that do similar thing, but more of it. But that understanding comes from lab experiments in a petri dish, and things that work in a petri dish might not work in the actual human, since living organism is complex and has many different chemicals and feedback loops.
Also, sometimes a drug is developed for one purpose, and it’s found that it’s possibly suited for another purpose. A example would be sildenafil was originally synthesized and studied to treat hypertension (high blood pressure) and angina pectoris (a form of cardiovascular disease). They found that it ‘accidentally’ gave erection to their test group, and as they say, the rest is history.
Sildenafil is the chemical name for Viagra.
It is not so important to know the mechanism of how it works just as long as it works. It is very hard to figure out exactly how every drug works in the body. But it is not that hard to just try a range of different drugs to see what they do. And then when you find a drug which works for a specific medical problem you prescribe it to patients.
In order to find a new drug what you would typically do is to look at all the other drugs which have been experimented with. There are similar chemical structures to the different drugs so you can start to see some patterns. Some chemical structures affect some areas of the body, and some diseases looks to be connected to these parts of the body. You can just synthesize different drugs with similar chemical structures and then start experimenting. First you experiment on animals, both to see if they are safe and to see if you can see any changes in them. Then you run a limited trial on a few subjects. If it looks promising and safe you run a full scale study.
I guess it depends on what you mean by work. There are a few key neurotransmitters in the brain that will make people feel and act different when you change those levels in the brain.
So lets consider depression as the example. We know stuff like serotonin can make people more satisfied. So maybe increasing serotonin levels will help with depression. It’s kind of a blunt force tool that has some beneficial outcomes. But it’s not really fixing the underlying problem.
>In short, there exists no rigorous corroboration of the serotonin theory, and a significant body of contradictory evidence
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>The impact of the widespread promotion of the serotonin hypothesis should not be underestimated. Antidepressant advertisements are ubiquitous in American media, and there is emerging evidence that these advertisements have the potential to confound the doctor–patient relationship.
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>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/
Stuff like SSRIs blunt all emotional feeling in many users. It will result in people losing their libido, etc.
So think of these drugs like painkillers. We have studies knowing they blunt pain, but they aren’t fixing any underlying issue or chemical imbalance.
Basically we are playing around in the dark seeing what works or not.
We generally only have an “educated guess” as to what causes a particular condition (particularly psychiatric conditions like ADHD). In the case of norepinephrine, it was believed to be a possible way to treat ADHD because most stimulants (that act on dopamine) also acted on norepinephrine. Ultimately they didn’t care of Atomoxetine increased norepinephrine levels, they cared if it treated ADHD symptoms. So they did trials to determine if it treated ADHD symptoms, and may not have had enough evidence to specifically prove that it increased norepinephrine levels.
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