Chemical difference between benzodiazepines and zopiclone (z-drugs)?

[JohnBoy2000]

Via

https://en.wikipedia.org/wiki/Zopiclone#Pharmacology

Zopiclone and benzodiazepines bind to the same sites on GABAA-containing receptors, causing an enhancement of the actions of GABA to produce the therapeutic and adverse effects of zopiclone

Zopiclone, although molecularly different from benzodiazepines, shares an almost identical pharmacological profile as benzodiazepines, including anxiolytic properties. Its mechanism of action is by binding to the benzodiazepine site and acting as a full agonist, which in turn positively modulates benzodiazepine-sensitive GABAA receptors and enhances GABA binding at the GABAA receptors to produce zopiclone's pharmacological properties

Benzodiazepine - Wikipedia

en.wikipedia.org

Nice breakdown of benzo's specifically.

What I'm getting is essentially they activate GABA to varying degrees, cause nerve depolarizations and thus signalling, to varying degrees.

Zopiclone is called "non-benzo" due to molecular structure, but as above, pharmaco profile is almost identical to benzo's.

Sound about right?

Why is it not considered as addictive as benzo's then?

 

[Rectify]

Because it is, structurally and pharmacologically, more of a sedating, slightly trippy tryptamine. Trytpamines are not addictive.

 

[JohnBoy2000]

Because it is, structurally and pharmacologically, more of a sedating, slightly trippy tryptamine. Trytpamines are not addictive.

Zopiclone VS Tryptamine VS Benzo:​

​

Granted I'm no organic chemistry authority, but honestly it looks closer to a benzo to me.

And it has no affect on tryptamine receptors, acts distinctly on benzo binding sites, identical to benzo's.

 

[Rectify]

Think About This Molecule Then.

JOHNBOY_2000
indole-3-yl-oxycarbonyldimethylamine

 

[Hippy Flower Fairy]

Zopiclone is really addictive, I was addicted to them on and off for years, different withdrawal, but still similar, but harder to wean off due to the short half life of zopiclone, I don't know what's worse to come off, I was depressed as fuck the last time I was on zopiclone, to the point I told my doctor to stop my repeat, flushed loads away and moved back on to benzos, which I've also been of and on for years, but I won't touch zopiclone again, evil fucking things

 

[dalpat077]

Sound about right?

Correct (short of getting into a discussion re: different GABA-A receptor subtypes and z-drug binding selectivity).

Why is it not considered as addictive as benzo's then?

I'd not be too sure on this one. I think that this was the hope and the intention but the reality seems to be turning out differently.

There's more than a few studies that have been done in recent years that suggest that they're every bit as addictive as benzodiazepines and with the same potential for abuse, physical dependence, and withdrawal. The study below sums it up really nice (and it's fairly recent i.e. 2019 and based on data collected between 2003 and 2017).

An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions

AbstractBackground. Although originally marketed as safe alternatives to the habit-forming benzodiazepines, growing numbers of zaleplon, zolpidem, and zopiclone

academic.oup.com

"Z-drug withdrawal symptoms, typically associated with the abrupt cessation of long-term, high-dosage intake, may include insomnia, anxiety, euphoria irritability, tremor, inner restlessness, speech difficulties, abdominal pain, hypertension, tonic-clonic seizures, and confusion/disorientation/delirium"

Reads a lot like benzodiazepine withdrawal to me!

Because it is, structurally and pharmacologically, more of a sedating, slightly trippy tryptamine.

This is utter garbage. Tryptamines are not even in the same chemical class as benzodiazepines and z-drugs.

No offense.

And it has no affect on tryptamine receptors, acts distinctly on benzo binding sites, identical to benzo's.

Correct once again.

Benzodiazepines and z-drugs: agonists at benzodiazepine sites on the GABA-A receptors and classed as sedatives.

Tryptamines: partial agonists at 5-HT2 (2A and 2C) receptors and classed as psychedelics.

Or is it just upgraded to be more sedating

Z-drugs are indicated for the treatment of insomnia (they're all sleeping pills) (although there's a fair amount of squabbling about their effectiveness for the treatment of anxiety but that's another story). I wouldn't use the word "upgraded" but rather "selective (binding)" (as noted above).

for more profit or monetary gain. Or is it just cheaper to manufacture.

Don't be so suspicious of the pharmaceutical industry! If anything they were meant to be an improvement and less harmful. Same as benzodiazepines replacing barbiturates (arguably they got this one right from a safety and life threatening point of view although I'm not so sure from an abuse and physical addiction point of view).

 

[Rectify]

And, Although The Dow Of Heaven Is Pointed, It Harms No One.

 

[ChemicallyEnhanced]

Via

https://en.wikipedia.org/wiki/Zopiclone#Pharmacology

Benzodiazepine - Wikipedia

en.wikipedia.org

Nice breakdown of benzo's specifically.

What I'm getting is essentially they activate GABA to varying degrees, cause nerve depolarizations and thus signalling, to varying degrees.

Zopiclone is called "non-benzo" due to molecular structure, but as above, pharmaco profile is almost identical to benzo's.

Sound about right?

Why is it not considered as addictive as benzo's then?

It is. My G.P. actually referred to Zopiclone as "the new diazepam" as in it was initially thought of as safe and having a very low addiction profile and now they're seeing people have HUGE problems trying to come off it. The reasons it is considered "less addictive" is because it is prescribed once a day and lasts about 7 hours. So it doesn't get you AS physically dependant AS quickly since it's unusual to have a consistent amount of it in your system. However, if you were to take it multiple times a day like with some benzo's, you'd suffer the same symptoms upon abrupt cessation.

 

[Jen X]

I don't find then similar at all. Zopiclone just put me to sleep and leave a metallic taste in my mouth and i have never heard a doctor use them for anxiety, just sleep. Benzos can put someone to sleep but they treat anxiety without putting you to sleep.

 

[Hippy Flower Fairy]

However, if you were to take it multiple times a day like with some benzo's, you'd suffer the same symptoms upon abrupt cessation

Thing is once you start taking them at night, and then effect wears off, you start getting anxiety, or worsening anxiety in the day, so people start taking them in the day too as they do help anxiety, by this point one doesn't stop some people to sleep, I'd take a few at night then one or two in day too, as like I said short half life

And there's so many story's like mine of how additive they are and how hard to come off, needing switched to valium just like coming off shorter acting benzos, people switch to valium for its long half life then taper from that, if your doctor knows his shit that's what he'll do, if your doctor is a dick he'll think tapering off zopiclone will work, maybe for some it will but not for most people

 

[ChemicallyEnhanced]

Thing is once you start taking them at night, and then effect wears off, you start getting anxiety, or worsening anxiety in the day, so people start taking them in the day too as they do help anxiety, by this point one doesn't stop some people to sleep, I'd take a few at night then one or two in day too, as like I said short half life

And there's so many story's like mine of how additive they are and how hard to come off, needing switched to valium just like coming off shorter acting benzos, people switch to valium for its long half life then taper from that, if your doctor knows his shit that's what he'll do, if your doctor is a dick he'll think tapering off zopiclone will work, maybe for some it will but not for most people

I agree. And no, my doctor doesn't think that. He was just saying how when it was first introduced it was thought it would be easy to just stop taking, people he see's patients who can't just stop or even taper slowly. I don't know how he helps hem, though. It's never prescribed for more than 14 days here and also they STRONGLY advice you to only take it ever other night.
He prescribes it to me periodically when my other sleep meds aren't working and he'll usually give me 6 of them and say to take a night off between each dose.

 

[Hippy Flower Fairy]

It's never prescribed for more than 14 days here and also they STRONGLY advice you to only take it ever other night

Yeah I was only priscribed 10 a month and told to only take when needed,then it went up to 14 when I came off mirtazapine as that helps sleep, I got told to take the zopiclone every other night, obviously I couldn't sleep without anything as by then I'd take 2, 3 or 4 zopiclone a time then my mirtazapine ontop and on the nights I didn't have any zopiclone left, so bought more online, I'd go between benzos, mirtazapine, promethazine and zopiclone and trying not to get addicted to one, but now I can't sleep without anything, but I'm doing a self taper as doctors are useless when it comes to getting you off pills

 

[ChemicallyEnhanced]

Yeah I was only priscribed 10 a month and told to only take when needed,then it went up to 14 when I came off mirtazapine as that helps sleep, I got told to take the zopiclone every other night, obviously I couldn't sleep without anything as by then I'd take 2, 3 or 4 zopiclone a time then my mirtazapine ontop and on the nights I didn't have any zopiclone left, so bought more online, I'd go between benzos, mirtazapine, promethazine and zopiclone and trying not to get addicted to one, but now I can't sleep without anything, but I'm doing a self taper as doctors are useless when it comes to getting you off pills

Same. I haven't slept without some form of sedation for 12 years.

 

[Hippy Flower Fairy]

Same. I haven't slept without some form of sedation for 12 years

That's more than twice as long as me, I occasionally go through stages of coming off pills and sleeping without anything, but it's horrible, the withdrawal the insomnia, then sleeping okay for a little while but in the end insomnia is back and I lay awake for hours, and end up back on pills, fucking hell it's shit ain't it

 

[ChemicallyEnhanced]

That's more than twice as long as me, I occasionally go through stages of coming off pills and sleeping without anything, but it's horrible, the withdrawal the insomnia, then sleeping okay for a little while but in the end insomnia is back and I lay awake for hours, and end up back on pills, fucking hell it's shit ain't it

The worst!

 

[Sk1500]

I find my tolerance with zopiclone very quickly becomes very high, plus as I find not sleeping triggers my anxiety incredibly quickly, it is one of the only medications that I find GPS monitor extremely closely and only generally give me for 4 weeks max, haven't had in at least 5 years though.

There very tough to get the proper sleeping benzos from the gp, I think I've only ever had Nitrazepam maybe 5 or 6 times and thats been 2 or 3 days tops. Diazepam I always end up on a very high dose, currently down to 40mg and unless I run out for few days I don't notice it (been up to 70 prescribed for over a year and was having to get extra), plus it's one I'd take generally during daytime, although if your relaxed. That's the hardest medication I think I came off of, took about 4 years weaning but unfortunately only lasted 18 months and been back on it over a year.

Mirtazapine and quetiapine, both similar to me, knocked me out the most and took long time to build up tolerance, plus I found very easy to stop very quickly......all good except I put on masses of weight on both.

Melatonin didn't do anything for me, even though in theory should be 1 of the best ones, plus if I remember it either changed to a CD or a secondary care only prescription, not through GP.

They like to try antidepressants that will eventually possibly help with sleep. Unfortunately that's not much use if you haven't slept in few days and feel like 1 more night awake will drive you mad.

Some of the antihistamines work well, bit too smashed to think which ones of the top of my head. Cyclizine works brilliantly but you need to go in with either listing vertigo symptoms or sickness.

Seems like America offers a much wider range than the UK.

Wouldn't wish bad insomnia on anyone. Hope anyone can get it sorted. I know I'm missing lots of others but can't think at the minute. If you don't have bad side effects, like weight gain, I think the best options are mirtazapine, Quetiapine or Cyclizine

 

[izo]

zopiclone is very different from a tryptamine structurally. i found it to be much more creepy than normal benzodiazepines. pagoclone on the other hand is an isoindole and zolpidem is much more similar to tryptamines than zopiclone:

 

[OpiumWDsoldier]

Correct (short of getting into a discussion re: different GABA-A receptor subtypes and z-drug binding selectivity).



I'd not be too sure on this one. I think that this was the hope and the intention but the reality seems to be turning out differently.

There's more than a few studies that have been done in recent years that suggest that they're every bit as addictive as benzodiazepines and with the same potential for abuse, physical dependence, and withdrawal. The study below sums it up really nice (and it's fairly recent i.e. 2019 and based on data collected between 2003 and 2017).

An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions

AbstractBackground. Although originally marketed as safe alternatives to the habit-forming benzodiazepines, growing numbers of zaleplon, zolpidem, and zopiclone

academic.oup.com

"Z-drug withdrawal symptoms, typically associated with the abrupt cessation of long-term, high-dosage intake, may include insomnia, anxiety, euphoria irritability, tremor, inner restlessness, speech difficulties, abdominal pain, hypertension, tonic-clonic seizures, and confusion/disorientation/delirium"

Reads a lot like benzodiazepine withdrawal to me!



This is utter garbage. Tryptamines are not even in the same chemical class as benzodiazepines and z-drugs.

No offense.



Correct once again.

Benzodiazepines and z-drugs: agonists at benzodiazepine sites on the GABA-A receptors and classed as sedatives.

Tryptamines: partial agonists at 5-HT2 (2A and 2C) receptors and classed as psychedelics.




Z-drugs are indicated for the treatment of insomnia (they're all sleeping pills) (although there's a fair amount of squabbling about their effectiveness for the treatment of anxiety but that's another story). I wouldn't use the word "upgraded" but rather "selective (binding)" (as noted above).



Don't be so suspicious of the pharmaceutical industry! If anything they were meant to be an improvement and less harmful. Same as benzodiazepines replacing barbiturates (arguably they got this one right from a safety and life threatening point of view although I'm not so sure from an abuse and physical addiction point of view).

friend... look what they did with OxyContin. That was just pure evil, and look at the mess in created. Heroin and fentanyl deaths everywhere. all started for most ppl with that stupid pill. They said it was non-addictive. Idk how that they could even say that since it obviously is. But you should be suspicious of them. its about money not health. Seroquel is another example, or Haldol. These drugs are toxic, yet they give them out like candy. Also why lawsuits occur regarding these dangerous drugs. but if they made more of a profit off of the sale than the loss in court then its a good deal for them. thats how they operate. one of the most corrupted industries in the world. The word "pharmaceia" (i think thats how you spell it) also means poison or spell portions, the root word. So we in effect are go to our pharmacies, the poison substance store.

The world has been deceived in so many ways.

Oh and when they came out with OxyNeo... That was just a clever way of getting another patent for another 20 years so nobody could use the formula. Nothing to do with saving ppl from injecting or abusing the drug, that was just a reason to change to formula to something new for another monopoly on the pill. Wicked wicked ppl these pharma companies

Same reason why they cant cure cancer but ayervedic doctors can. money money money, and theres no money in a cure, but lots in maintenance treatments and palliative care. again... evil

 

[dalpat077]

look what they did with OxyContin

Yeah. I was waiting for this to come up! I'm surprised it took so long!

All jokes aside though:

I'm of the personal opinion that you cannot lay the opioid crisis squarely at the feet of Purdue and OxyContin. It had the groundwork being laid for it starting as far back as 1980. Look up "studies" e.g. Porter and Jick (1980) or Russell Portenoy and Kathleen Foley (1986). Also Dr. James Campbell and the American Pain Society (1995/1996). Arguably certain medical professionals or "experts" and various associations and regulators are just as responsible.

The problem with all of this stuff is that it takes years in order for adverse side-effects to become known and statistically significant. Clinical trials can only prove so much and cannot predict outcomes far into the future. Think of Thalidomide as an example. And there's probably dozens and dozens of other examples over the years. Bayer and Heroin another that comes to mind.

Of course there's the ever so unpalatable argument (usually made by me) as to the medical benefits of some of these pharmaceuticals vs. the statistical significance on the destruction that they can cause. Fentanyl is a prime example of an invaluable pharmaceutical with a wide therapeutic index and range of applications and was an improvement on morphine and meperidine (and later phenoperidine). Point being: it too needs to be seen in perspective. It wasn't researched and formulated in order to simply unleash it on Joe Public and create a captive market for guaranteed profits.

I suppose the point of my ramblings above: big pharma. is indeed big business. But I personally don't know of any pharmaceutical that's been specifically formulated and marketed to Joe Public purely in the interests of profit with a blatant disregard for its harmful side-effects and/or addiction potential (at least not initially anyway and this is the key). Could/should more care be taken and could/should there be more oversight? Probably the answer is yes in both cases. But I wonder at what cost that would come at insofar as innovation and progress is concerned.

i found it to be much more creepy than normal benzodiazepines

^ That gave me a good laugh (the wording anyway)!

I have to admit that I envy you dudes who understand this shit on a molecular level. Now if I had my time over...

If I may comment i.e. this not my thread:

Great posts here and a great thread and I'm pleased it was started.

These z-drugs don't seem to be given their due attention. The impression I get is that they're almost perceived as being almost benign when compared to benzodiazepines. It's simply untrue. But it's taken a few years for their adverse side-effects to become known and statistically significant (as already alluded to above).

 

[dalpat077]

Oh and when they came out with OxyNeo... That was just a clever way of getting another patent for another 20 years so nobody could use the formula. Nothing to do with saving ppl from injecting or abusing the drug, that was just a reason to change to formula to something new for another monopoly on the pill. Wicked wicked ppl these pharma companies

Same reason why they cant cure cancer but ayervedic doctors can. money money money, and theres no money in a cure, but lots in maintenance treatments and palliative care. again... evil

Oh and you edited your post while I was busy with my response above! Wicked and evil!

May I ask a dumb question? How is it the responsibility of the pharmaceutical industry to save people from injecting or abusing a drug? Matter of fact and if these forums are anything to go by: they actually go out of their way to try and ensure that this doesn't happen (or make it very difficult to accomplish anyway).

The argument here (well my argument anyway) is NOT that they're NOT out to make money. They are. There's no doubt about that. But to suggest that they make addictive substances simply to stay ahead of the game is ludicrous to me. I think you're getting them confused with street dealers!

With regard to OxyNEO® (note the registered trademark symbol! ): it was a reformulation of OxyContin® into a version with tamper-resistant properties and to make good on the promise of it being controlled or extended release to be taken only every 12 hours. What more do you want?

As for curing cancer: well if you do get cancer, and after you've been to one of your Ayurvedic doctors, rest assured that Fentanyl (or another terrible, horrible, wicked, and evil opioid) will be made available to you for pain (courtesy of big pharma.)!