Alexis Fernandez-Preiksa

casually be taking for medical purposes even at the time.

But initially doctors loved Quaaludes so much or methoqualone because they were really, really desperate to find an alternative to barbiturates because barbiturates had this really small therapeutic window and they were used to treat insomnia, anxiety, seizures to also induce anesthesia by acting as sedatives and hypnotics.

But also they were dangerous due to like a really high risk of addiction, fatal overdoses and also really, really bad withdrawals.

Now, when we talk about a small therapeutic window, it means that the dose that's required for sedation is really dangerously close to the same that that dose that could stop you from breathing so that the window where it works for its intended purpose is small, therefore making it dangerous.

Methaquiline was introduced as like a supposedly safer pharmaceutical option.

And because of that, it exploded in popularity.

But it's actually not that safe at all.

Now, let's first talk about the mechanism of action.

It acts as something called a positive allosteric modulator of the GABA-A receptor.

Let's break that down because what the fuck am I talking about?

So it doesn't replace GABA.

When we talk about allosteric binding site or an allosteric modulator, you have different binding sites on a receptor within the brain, okay?

So...

If something binds to the allosteric site, it can enhance or diminish the activity of the main molecule that's going to bind on that site.

So let's say GABA is the molecule that's binding on this site.

The allosteric site is not where GABA is binding.

So you can then bind something onto that site, not compete with where GABA binds to.

And you can turn up or turn down what's going on.

So when we talk about a positive allosteric modulator, it is modulating the activity of GABA not competing with.

And in this case, it is increasing the effects of endogenous GABA.