December 8, 2022

The result of research to develop a nonaddictive cough suppressant produced dextromethorphan. It was FDA approved in 1954 but the pharmacology of this cough suppressant is complex.

What’s up everybody dr rossi shrinks and today i’m going to cover a new medication monday topic the combination of dextromethorphan and bupropion also known as axo5 so the result of the research to create a non-addictive cough suppressant resulted in the production of dextromethorphan now this is a common medication that’s available over the counter in

Most cases and something that you know is been around since the 1950s it was actually fda approved in 1954 but the car the pharmacology of this medication is actually quite complex and there’s been a renewed interest in it as a potential psychiatric medication so let’s go into how this functions and a little bit about why it may be a good medication for psychiatry

To revisit so dextromethorphan functions as what we call an uncompetitive nmda glutamate antagonist so that’s complicated i’ll break it down a little more so nmda glutamate blockers are things like ketamine right this is one of the mec proposed mechanisms by which ketamine helps treat depression so naturally you can already see dextromethorphan having a similar

Having a similar mechanism of action may help treat depression now it also has a little bit of other benefits from a psychiatric perspective and that is called sigma 1 stimulation so sigma 1 is another receptor that’s sometimes stimulated by certain psychiatric medications it’s been helpful in things like depression and then it also acts as a serotonin reuptake

Inhibitor so three things that could potentially benefit uh someone taking dextromethorphan who has a psychiatric disorder namely depression so it should become clear now why this medication again people are renewed interest in it and why it might be a good thing to look at now here’s where it becomes interesting because you might say well okay why don’t we

Just use dextromethorphan by itself why do we have to add bupreprion to the mix so bupreprion as i’ve covered in previous videos is a medication that’s been around since 1985 i believe it was fda approved for depression and it is a norepinephrine dopamine reuptake inhibitor so this is going to block the reuptake of norepinephrine and dopamine thus increasing

Norepinephrine and dopamine levels so it’s currently used to treat depression like i said also seasonal affective disorder also nicotine dependence so anyone that has those three conditions these are sort of the fda approvals for it now recent research has revealed something interesting though and that is that bupropion is what we would call an inhibitor or potent

Inhibitor of the cytochrome p450 2d6 enzyme right so it doesn’t really this doesn’t really matter in a long discussion on cytochromes in in what they do etc is probably beyond the scope of this short video but the bottom line is that cytochrome p450 and specifically 2d6 is the is the enzyme that’s going to metabolize dextromethorphan so what this is going to be

Doing is by combining bupropion with the dextromethorphan you’re going to allow dextromethorphan to be around for a longer period of time that’s what it’s going to do it’s going to delay the breakdown of that medication so a little bit beyond the scope at some point we’ll discuss p450 system but for now just know that this 2d6 enzyme metabolizes dextromethorphan

And one of our goals here is to prolong the length of time that decrement orphan will be active in the body to do that we use bupropion which is going to block that enzyme that’s metabolizing it now the combination of these two drugs would be 45 milligrams of dextromethorphin along with 105 milligrams of bupropion two times per day and that creates your ax 05

Medication the proposed mechanism like i’ve already said is to sort of prolong destroy methods activity by inhibiting 2d6 but there’s also the added benefit rate of destroyment orphan having sigma 1 stimulation as well as serotonin reuptake inhibition and you get the added benefit of bupropions norepinephrine and dopamine reuptake inhibition so combining all these

Things together that’s what creates the antidepressant effect and that was what was seen in a phase three randomized controlled trial where they looked at patients with mdd and they found that axo5 outperforms placebo when you start looking at depression rating scales so it’s better than placebo it’s proven in a randomized controlled trial that lasted six weeks

And um and this is something that’s on potentially on the horizon as a medication to treat depression so we’ll see where it goes again interesting i always think it’s good to go back and look at medications that have previously been uh used or may have properties that have recently been discovered for benefits with depression or other psychiatric disorders so

That concludes the video on the combination of dextromethorphan and bupropion if you guys like the channel please subscribe and if you have comments or questions about this new medication drop them below and i’ll try to answer them

Transcribed from video
New medication Monday: Combination Dextromethorphan and Bupropion AXS-05 By Shrinks In Sneakers