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Misc nonbenzodiazepine hypnotics - why they stop working after awhile?

^I've heard of olanzapine causing similar and other negative side effects, such as increasing risks for diabetes and other nasty things.

Of all the antipsychotics, I would put olanzapine pretty damn low on my list of preferred APs, but most people probably don't agree with my prefered APs (typicals).
 
olanzapine only increases your susceptibility to diabetes by 50% (at least thats what all the doctors i've asked said) but of all the anti psychotics it's probably the worst when it comes to weight gain
 
Nice! wouldn't mind having boobs i'd give them a real good feel up amongst something else, seriously though that's fucked up & diabetes 50% is pretty bad never helped anyway see ya later olanazapine :D
 
It's kind of misleading to call them nonbenzodiazepines, since they basically try to mimic benzodiazepines in every way possible, working on the same receptors and all.
Although they are an agonist of the same type of receptors as benzodiazepines ( the GABA-A receptors), the exact subunits of the GABA-A receptors which zolpidem and benzos bind to vary quite a bit between the two. Here's some info on the subject:
Zaleplon and Zolpidem both are agonists at the GABA A ɣ 1 subunit. Due to its selective binding, Zolpidem has very weak anxiolytic, myorelaxant, and anticonvulsant properties but very strong hypnotic properties. Zolpidem binds with high affinity and acts as a full agonist at the α1-containing GABAA receptors, about 10-fold lower affinity for those containing the α2- and α3- GABAA receptor subunits, and with no appreciable affinity for α5 subunit-containing receptors

Zolpidem has a tenfold higher affinity for α1 than α2 and α3; this is very different from most benzodiazepines, which don't have such a large difference between their α1 affinity and α2/α3 affinity. Its also worth noting that the "Big Three" benzos (alprazolam/Xanax, diazepam/Valium, and clonazepam/Klonopin) have a higher affinity for α2/α3 than α1; binding to α2/α3 produces much more anxiolytic effects (and hence, higher potential for addiction), where as α1 produces greater hypnotic effects (hence, zolpidem is better for sleep, as well as being less addictive).

Although zolpidem is still physically (and slightly psychologically) addictive nonetheless, it is far, far less addictive than benzodiazepines.
When I was going through my benzo and zolpidem phase about 5 years ago, I remember zolpidem still producing the same effects at the same doses for weeks (perhaps months) -- I also did not keep want to taking more of it after the effects had worn off (the physical side effects at higher recreational doses deterred me from taking it more than once every 1-2 days, but it was still entertaining to use). However, I remember my dose of benzos doubling after about 10 days, and then quadrupling after a month -- eventually, the effects of benzos became just a "background feeling". I believe this is due to the half-lives of benzos being so massive, that tolerance is simply unavoidable.
With zolpidem's short half-life of 2-3 hours, tolerance has a much slower onset, and withdrawals/tolerance would mostly be limited to difficulty sleeping - where as benzos produce much more harsh withdrawal symptoms such as anxiety, malaise, and in some cases seizures.

To become physically dependent to zolpidem, one would literally have to work at it. Taking at least 4-6 doses a day. Otherwise, the risk of taking zolpidem every day is pretty much limited to difficulty sleeping.

I agree however that it shouldn't be marketed as "non habit forming"; but when compared to benzos, it is less habit forming (albeit still "habit forming"). Zolpidem is also not meant to be taken every night; it is meant for short term use (less than a month) to merely get a person's sleep schedule back on track, or to be taken only occasionally during severe episodes of insomnia. If a doctor is giving a patient a long-term once a day prescription to zolpidem, they aren't prescribing it correctly and its almost malpractice.
 
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If a doctor is giving a patient a long-term once a day prescription to zolpidem, they aren't prescribing it correctly and its almost malpractice.

Lol, no it's not.


Quote from package insert.
"Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. The treatment should be as short as possible. Generally the duration of treatment varies from a few days to two weeks, with a maximum, including tapering off process, of four weeks. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient’s status."



But I do get what you are trying to say.
 
Yeah, it's definitely NOT illegal, though it could be unethical. My friend was prescribed Zolpidem, but the extendend release formula and the instant release formula, for five years straight, and I've known many people prescribed benzodiazepines for many, many years.

IME zolpidem isn't very effective for sleep. Alprazolam is far better IMO, though its also a lot more dangerous due to its dependency risk. My problem with zolpidem is that even when I close my eyes, I won't fall asleep in time to avoid the drugs bizzare, wonky 'buzz', and I'll often find myself getting up, and walking around, talking to myself.

However, the answer to this thread is that Z-drugs, like benzo's stop working at the same dose, due to tolerance. I'll keep this open a bit longer to see if anything more comes out of it, but the questions been answered many times over.
 
Although they are an agonist of the same type of receptors as benzodiazepines ( the GABA-A receptors), the exact subunits of the GABA-A receptors which zolpidem and benzos bind to vary quite a bit between the two. Here's some info on the subject:
Zaleplon and Zolpidem both are agonists at the GABA A ɣ 1 subunit. Due to its selective binding, Zolpidem has very weak anxiolytic, myorelaxant, and anticonvulsant properties but very strong hypnotic properties. Zolpidem binds with high affinity and acts as a full agonist at the α1-containing GABAA receptors, about 10-fold lower affinity for those containing the α2- and α3- GABAA receptor subunits, and with no appreciable affinity for α5 subunit-containing receptors

Zolpidem has a tenfold higher affinity for α1 than α2 and α3; this is very different from most benzodiazepines, which don't have such a large difference between their α1 affinity and α2/α3 affinity. Its also worth noting that the "Big Three" benzos (alprazolam/Xanax, diazepam/Valium, and clonazepam/Klonopin) have a higher affinity for α2/α3 than α1; binding to α2/α3 produces much more anxiolytic effects (and hence, higher potential for addiction), where as α1 produces greater hypnotic effects (hence, zolpidem is better for sleep, as well as being less addictive).

Although zolpidem is still physically (and slightly psychologically) addictive nonetheless, it is far, far less addictive than benzodiazepines.
When I was going through my benzo and zolpidem phase about 5 years ago, I remember zolpidem still producing the same effects at the same doses for weeks (perhaps months) -- I also did not keep want to taking more of it after the effects had worn off (the physical side effects at higher recreational doses deterred me from taking it more than once every 1-2 days, but it was still entertaining to use). However, I remember my dose of benzos doubling after about 10 days, and then quadrupling after a month -- eventually, the effects of benzos became just a "background feeling". I believe this is due to the half-lives of benzos being so massive, that tolerance is simply unavoidable.
With zolpidem's short half-life of 2-3 hours, tolerance has a much slower onset, and withdrawals/tolerance would mostly be limited to difficulty sleeping - where as benzos produce much more harsh withdrawal symptoms such as anxiety, malaise, and in some cases seizures.

To become physically dependent to zolpidem, one would literally have to work at it. Taking at least 4-6 doses a day. Otherwise, the risk of taking zolpidem every day is pretty much limited to difficulty sleeping.

I agree however that it shouldn't be marketed as "non habit forming"; but when compared to benzos, it is less habit forming (albeit still "habit forming"). Zolpidem is also not meant to be taken every night; it is meant for short term use (less than a month) to merely get a person's sleep schedule back on track, or to be taken only occasionally during severe episodes of insomnia. If a doctor is giving a patient a long-term once a day prescription to zolpidem, they aren't prescribing it correctly and its almost malpractice.

Ya very interesting post. I disagree about the last bit regarding long term use of benzos in those who need it, but I agree with the rest.

The far superior benzodiazepine drug triazolam is available for those like me who prefer a super short acting hypnotic. Oh and it's like 80x more potent if my maths is correct? 0.25mg Triazolam = 20mg zolpidem.
 
Yeah, that sounds right man, cause I'm fairly positive that triazolam is 2x the strength of alprazolam, and I know that 20mg of zolpidem is equivalent to .5mg of alprazolam.
 
i thought triazolam was roughly 4x the strength of alprazolam. when i got it prescribed, i almost never used it for sleep, as it works really well for anxiety and panic attacks, but at the juncture i was seriously desensetized to benzos in general. of all the hypnotics i tried, i found triazolam, flunitrazepam and midazolam to be the only ones that rival alprazolam in terms of anxiolysis.
 
Do NMDA antagonists dosed 30 minutes before taking a Z-drug or benzodiazepine reduce the physical dependence and tolerance from increasing, as they do partially with opioids?
 
Do NMDA antagonists dosed 30 minutes before taking a Z-drug or benzodiazepine reduce the physical dependence and tolerance from increasing, as they do partially with opioids?

Why would that be true for GABAergics just because it is somewhat, negligible IMHO, effective at slowing tolerance. Benzos and z-drugs have virtually no similarities to opiods. NMDA agonist don't have any effect of modulation of bzd alpha receptors 1&2.
 
Why would that be true for GABAergics just because it is somewhat, negligible IMHO, effective at slowing tolerance. Benzos and z-drugs have virtually no similarities to opiods. NMDA agonist don't have any effect of modulation of bzd alpha receptors 1&2.

I'm fully aware of the differences between GABAergics, like benzos (positive allosoteric modulators; agonists at the BZD receptors), and opioids, lol. It's not the modulation of opioid receptors that causes Dextrorphan (DXM's NMDA antagonist metabolite) or memantine or any other powerful (voltage-independent) NMDA antagonist to reduce tolerance. Even weaker (voltage dependent) NMDA antagonists like Zn and Mg partially prevent tolerance from increasing, with dextroamphetamine and opioids, in my experience, and amphetamines and opioids are nothing alike.

Cutting out calcium supplements and adding chelated Magnesium supplements would be the first place to start to give you adequate antagonism of the NMDA receptors.
 
I wasn't saying you were uninformed.. But the notion that it would have any effect whatsoever seems incredibly far fetched. NMDA agonists have overlapping neurological binding sites and a similar mechanism of action to that of opiods, see methadone, it has weak NMDA activity. Benzodiazepines have absolutely not similarities as far as mechanism of action and metabolic pathways. They are in a class of their own, the only thing that's going to prevent toleranance is abstaining use and from a few articles I've read flumanezil. Although that seems like a dangerous way to reduce tolerance as it would cause precipitated w/d. Oddly enough, I just learned that many NSAIDs actually antagonism bzd receptors leading to diminished effects.

We need Sekio to answer this properly.
 
It's definitely far-fetched, but worth discussing, considering how many people are completely unaware of the benefits of tolerance increase-preventing drugs.

I just think that NMDA antagonists are seriously underrated in their abilities to treat psychiatric disorders, and if they also help tolerance from increasing, then that makes them useful tools for recreational users and non-abusing patients all the same. I had no idea that NSAIDs had any effect of the BZD receptors, that's pretty interesting and confusing at the same time. On that same note, ibuprofen has been demonstrated in studies to help prevent amp-induced neurotoxicity, which is partially caused and made worse through cerebral infammation, while naproxen didn't do much to help...

Paging Sekio now :)
 
This may be of some use to you peeps on Zolpidem, certainly has been for me!

Sublingual dosing of 3.5mg was equivalent to 10mg oral dosing.
At first I went all "poffycock" at it as it does use their brand names quite a bit, but I've tried it myself and it does provide a stronger effect.
But the half-life is shorter (and it's short enough!). Though this could be good for when you wake up in the middle of stupid o'clock and can't get back to yummy sleep without concussion.
 
First I want to thank everyone for their replies, you were all very helpful. I started this thread about non-benzodiazepine hypnotics, but I now realize that they do not work because my severe chronic pain neutralizes the hypnotic effects of all z-drugs. In any case instead of starting a new thread I thought I would just ask people about kratom since I am in severe pain and looking for all the help I can get and get the much needed sleep I need. There are so many websites where one could buy kratom but I don't know if any of these sites are any good ,or downright dangerous , so I would really appreciate people recommending the top kratom selling websites out their so I know I am getting good safe hi-quality kratom and not junk. Also since I have severe pain what kind of kratom would you recommend?

*snip* no sourcing and no source discussion

Kratom doesn't seem to come in capsules so I guess you have to buy empty capsules and then put the kratom in it or make tea with it, how do you guys ingest kratom? How good is it for pain to those of you who have tried it for pain?

Would really appreciate your replies as my pain doctor is a real hard ass stickler and I just can't live a normal life on the tramadol 50 mgs he has me on atm, but then again I have only saw him once so far. My pain is so bad that I have literally been bed-ridden for almost two years know. I have been on nearly every OTC and prescription NSAID ever made and none of them have helped with my pain. So I am hoping you guys can help me get the right kind of kratom for my severe chronic pain, even if kratom isn't all that strong I still need to give it a try because I need relief from my pain and suffering.

Need your help,
RBS
 
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Sorry NeighborhoodThreat. I don't sleep at all literally two hours a night or less and its not good REM sleep either, so sorry about forgetting the rules...but I just have one question why do the sysops have a problem with links to websites with LEGAL drugs on them? I mean its their site and they can do whatever they want with it but what harm is their in giving out links to legal drugs like kratom?
 
Yeah, that sounds right man, cause I'm fairly positive that triazolam is 2x the strength of alprazolam, and I know that 20mg of zolpidem is equivalent to .5mg of alprazolam.

what are you equivocating here? Level of sedation? Might as well be stating equipotent doses of alprazolam and diphenhydramine;
What I mean is, the effects of zolpidem vary so drastically from alprazolam that stating any equivalent doses between the two is sort of silly.
I don't start having extreme hallucinations and run around with double-vision chasing people's "evil twin" on alprazolam -- I don't think any dose of alprazolam would cause me to do that; I'd end up falling asleep before hallucinating.
Zolpidem, on the other hand, is an entirely different animal. The gap between its hypnotic effects and its "benzo-esque" effects (can't think of any other word to describe it) is so large, that zolpidem has to be placed in a class of its own separate from benzodiazepines.
Claiming equipotent dosages is just misinformation.
 
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