How Can I get Zopiclone-Lıke Effects (on my appetite)

[kimura]

Due to my severe insomnia, I have to use Zopiclone from time to time.
The drug may or may not be the best long term option for sleep and has a number of known issues, let us not get into those, because the thread will get of track in a hurry.

What I am wondering is why the day after my appetite is tremendously reduced. What is the mechanism of action here? I would love that sort of appetite suppression without having to take Zopiclone.

Please do not suggest random appetite suppressants, instead please just let us try and understand what chemical pathway is involved here and how it can be replicated with drugs that have less harsh side effects.

Thanks

 

[d1nach]

Does it make your mouth taste like metal like lunesta? That make me not wanna eat.

 

[kimura]

Does it make your mouth taste like metal like lunesta? That make me not wanna eat.

Yep it does
But the loss of appetite goes beyond that. The metallic taste is gone within 3-5 hours, but lack of appetite remains all day

 

[polymath]

Distortion of the sense of taste by chemicals is called dysgeusia. Zopiclone does cause the 'metal mouth' for me, too and it lasts for about 24 hours after the dose. It can probably also affect your taste in a more subtle way even after that, and decrease your appetite. Some bitter-tasting substances, including tonic water, can have an opposite effect of increased appetite (possibly because eating something will clear that bitterness from your mouth faster).

Alcoholics are familiar with everything tasting like crap when you've been drunk for several days in a row, and in that situation people can get almost all of their daily calories from the alcohol. It's some kind of reaction to your stomach getting irritated.

Maybe it's possible to alter the zopiclone molecule in some way that removes the benzodiazepine-like effect but keeps the dysgeusia. A new weight loss drug, possibly?

 

[d1nach]

Does it make you sleep longer than normal? If your going from idk 4-5 hours to 8-9 hours you might eat less and feel less hungry.

 

[kimura]

I really believe that the effect is neither due to dysgeusia or longer sleep.
Yes food will taste different for a few hours upon wakening but
1) this happens with other items as well and they do not reduce my appetite. You will know that food will not taste as good but internally you still have the drive to reach for food and put it in your mouth
2) The dysgeusia effect will last say 2-4 hours but the appetite suppression will last all day, well into the night even.

And there are tons and tons of things that will make me sleep longer -none of those will have the same appetite curbing effect at all

I am fairly certain that something more fundamental is happening in the brain

 

[polymath]

The Swiss Target Prediction app predicts that zopiclone can possibly bind to the orexin receptors, which regulate appetite. Other ways how some chemical compound can cause anorexia include cannabinoid receptor blockage and blood glucose elevation.

 

[kimura]

The Swiss Target Prediction app predicts that zopiclone can possibly bind to the orexin receptors, which regulate appetite. Other ways how some chemical compound can cause anorexia include cannabinoid receptor blockage and blood glucose elevation.

Oh Man
Tremendously helpful

Chances are the effect is not through glucose elevation or cannabinoid receptor blockage. I have reason to believe Zopiclone does not have either of these effects to any appreciable degree. I assume it is the Orexin pathway.

I know that a number of medicines for weight loss were being developed that worked through the Orexin receptor. Can you think of any obtainable drugs (prescription or OTC) that can similarly bind to the Orexin receptor?

 

[polymath]

Chances are the effect is not through glucose elevation or cannabinoid receptor blockage. I have reason to believe Zopiclone does not have either of these effects to any appreciable degree. I assume it is the Orexin pathway.

It's not certain at all, even though both zopiclone and the known orexin antagonist SB-408124 have some common structural features (aromatic nitrogen heterocycles, an amide nitrogen and a halogen substituent on an aromatic ring).

Zopiclone:

SB-408124:

 

[kimura]

polymath
Thank you so much
Actually I failed to give a proper account of what exactly was happening in my prior posts.
The effect of Zopiclone on appetite is extremely strange.

When you pop a pill it actually makes you extremely hungry. People often eat right before they fall asleep -and this effect is absolutely terrible, since you are eating in a half awake state and can consume enormous number of calories in a brief period of time. This part would make all the sense in the world, since Orexin will increase appetite -but then follow along below, where this theory fails to hold.

However the next day, appetite will absolutely be obliterated. This is very strange because the numbness and sleepiness will continue into the next day. But the appetite will be very much suppressed.

Now when you said that Zopiclone binds to the Orexin receptor, I assume it binds and blocks the receptor; i.e.works as an antagonist, because the current drugs in development that try to cure insomnia are OREXIN ANTAGONISTS.

But then how can a drug like Zopiclone both make you sleepy (it'd have to block Orexin to do this) while also making you hungry (it'd have to activate Orexin receptors to do this)???

Could it be that it works as an antagonist in the sleep center but as an Orexin agonist in the appetite control center of the brain?

Then, this brings up the question of how Zopiclone first increases appetite but the next day -for the entire day- reduces it. Could it be that it activates some receptor too much and makes you hungry at first, but then these receptors are temporarily downregulated for the next 16 - 24 hours? Again, if that is the case the target may or may not be Orexin -and it is certainly not having this particular effect on the sleep center.

 

[polymath]

^ The hungriness at the beginning could be caused simply by disinhibition, just like people go buy junk food after being in a pub. Assuming the orexin hypothesis (for which there is no real proof), the effect could change to opposite if the metabolites of zopiclone are antagonists at the orexin receptors and zopiclone itself is an agonist.

 

[kimura]

^ The hungriness at the beginning could be caused simply by disinhibition, just like people go buy junk food after being in a pub. Assuming the orexin hypothesis (for which there is no real proof), the effect could change to opposite if the metabolites of zopiclone are antagonists at the orexin receptors and zopiclone itself is an agonist.

There is perhaps some element of this, but a lot of medicines will cause disinhibition and even very potent ones that have a very strong disinhibition do not have this effect at all