Benzos of abuse

[haribo1]

I've been reading up on the abuse of the benzos. What I have noticed is that in the more abused ones, the amide is tertiary. The best example I can give is Nitrazepam vs. Nimetazepam. Nimetazpam is so popular in SE Asia that it has been withdrawn and if you buy it off a dealer, your most likely getting nitrazepam or such. The only difference being that in nimetazepam, there is an extra methyl on the amide. Of course, all the triazolo type benzos are tertiary and they all seem to be more euphoric than the secondary amides. Methyl seems to be the optimum substituant for activity (prazepam comes in 40mg tablets so it's a lot lest potent than, say, diazepam).

From these ill concieved ideas, I suggest that niphenazepam will be a)stronger & b)more euphoric. Of course, if you can purchase the intermediate (but still, I assume, active) norquazepam then forming the triazolo ring with acetyl hydrazine, then you should get something with decent potency.

 

[mad_scientist]

The tertiary amines do generally seem to be more preferred, but note that bromazepam, lorazepam and clonazepam are all secondary amines and seem to be very popular drugs.

Mind you, the N-methyl analogues of those three might well be better, as far as I'm aware only lormetazepam has been marketed and is reputed to be a more enjoyable drug than lorazepam itself.

I'd like to see the triazolo analogues of nitrazepam or bromazepam, either of those could be very promising, and relatively easy to make too.

Also for something a bit different I'm quite fascinated by imidazenil, a benzo thats highly selective for anxiolytic effects and has no sedative or amnestic action would be a very different profile than any of the benzos on the market, hard to say whether it would still be as much fun though.

 

[Ham-milton]

But do you suppose that those drugs are popular because they're more enjoyable or more available? Would kids be doing harder drugs today if pharmaceuticals weren't so available? I bet. "harder" is such a soft word.

 

[haribo1]

I think clonazepam is replacing diazepam because it's out of the system quicker, but boy does it suck. I would bet a pound to a penny that the methyl version is a lot beter. Bromazepam also sucks and again, it's prescribed more and more (in Frsnce) because it's less abusable.
I bet the N-methyl version of phenazepam is also a lot better.

 

[LivingOnValium]

I think lorazepam and lormetazepam (methyl lorazepam) have the same therapeutic dose range.

Jasoncrest might be able to tell us the difference and abuse of potential these two. Where he lives theý're both commercial.

 

[Ham-milton]

Any of these n-methyl's will be legal in the US. Sweet.

 

[jasoncrest]

I think lorazepam and lormetazepam (methyl lorazepam) have the same therapeutic dose range.

Jasoncrest might be able to tell us the difference and abuse of potential these two. Where he lives theý're both commercial.

Lormetazepam is quite a strong hypnotic benzo, very high recreationnal potential.

Lorazepam is just a weird cross between Zolpidem and a weaker version of Diazepam; a very mellow & mild (but still effective) anxiolytic.

-

Can someone please list some commercialized benzos and their methyl counterpart?
there's Nitrazepam -> Nimetazepam and Lorazepam -> Lormetazepam from what I understand, what are other exemples?

 

[LuxEtVeritas]

are the ethyl derivatives more potent than the methyls (if this was addressed my apologies)

 

[mad_scientist]

Can someone please list some commercialized benzos and their methyl counterpart?
there's Nitrazepam -> Nimetazepam and Lorazepam -> Lormetazepam from what I understand, what are other exemples?

Nordazepam --> Diazepam

Oxazepam --> Temazepam

Thats about the only others I can think of where both the methylated and non-methylated drug has been marketed separately.

 

[jasoncrest]

Nordazepam --> Diazepam

Oxazepam --> Temazepam

Thats about the only others I can think of where both the methylated and non-methylated drug has been marketed separately.

Then yeah, it's pretty obvious, the methyl group just makes more potent by weight, more sedative, and with a higher abuse potential.

Equivalent dosages:
Nitrazepam 10mg -> Nimetazepam 5mg
Lorazepam 2mg -> Lormetazepam 1mg
Nordazepam 15mg -> Diazepam 10mg
Oxazepam 30mg -> Temazepam 20mg

The methyl derivatives are all twice as potent by weight or 150% more potent.

-

Oxazepam and Nordazepam are some of the weakest, less abusable benzos, while their methyl counterparts, Diazepam and Temazepam belong to the 10 most commonly abused benzos in the world......

 

[hussness]

Are there any theories for why which benzos are more pleasant that aren't just extrapolations from behavioral stats? I mean anything pharmacologically based. The potency and rate of clearance of drug + active metabolites all have reasonable pharmacokinetic and pharmacodynamic explanations, as far as I know, but I have never heard a tenable argument for why some benzos are more euphoric than others. From reading trip reports, what benzos people like seems to be highly variable depending on the person. For instance, I love clonazepam, am fairly ambivalent about lorazepam, and ambien (which isn't a benzo) works better for my anxiety than anything else I know. It also, curiously, doesn't cause all that much sedation in me. Are these effects just idiosyncratic, or is there some kind of explanation for this?

 

[swilow]

Oxazepam and Nordazepam are some of the weakest, less abusable benzos,

Oxazepam sucks for anxiety, I found it basically ineffective. I was accidentally scripted it though so..... I don't get sleepy of zolpidem- more sketchy and scattered, but only for 30 minutes or so.

This is a basic question, but what are the metabolites of diazepam- I had thought its was nor-diazepam (?) and temazepam..?

I actually have never felt benzo's are that effective, for my anxiety at least....

 

[Riemann Zeta]

Indeed, they really aren't all that effective, at least for me. The anxiety is still there, I just don't give a shit (or at least, as much of a shit) about it for a half-life or two. Then the bitch is back, in full force. In my experience, benzos are like opioids, but they modulate fear and panic instead of pain. That is, although the 'pain' is still there--you can still sense its presence--it is numbed at both a physical and psychical level.

 

[iconic1]

after a few months of one benzo i take a month of a different one and rotate

 

[LuxEtVeritas]

Indeed, they really aren't all that effective, at least for me. The anxiety is still there, I just don't give a shit (or at least, as much of a shit) about it for a half-life or two. Then the bitch is back, in full force. In my experience, benzos are like opioids, but they modulate fear and panic instead of pain. That is, although the 'pain' is still there--you can still sense its presence--it is numbed at both a physical and psychical level.

''

also just like with pain if you let anxiety pass a certain threshold even valid drugs are far less effective and sometimes barely work at all until one gets to doses that are basically just stoning one out of their mind so it is more 'distraction' and disassociation (not classical per se) that will work

 

[Ham-milton]

Then yeah, it's pretty obvious, the methyl group just makes more potent by weight, more sedative, and with a higher abuse potential.

Equivalent dosages:
Nitrazepam 10mg -> Nimetazepam 5mg
Lorazepam 2mg -> Lormetazepam 1mg
Nordazepam 15mg -> Diazepam 10mg
Oxazepam 30mg -> Temazepam 20mg

The methyl derivatives are all twice as potent by weight or 150% more potent.

For recreational use, where potency really isn't that big of a deal (when we're talking about a drug that's active between 10 and 70mg), and euphoria is important, how does substituting a the 9-Fluoro or Chloro with a nitro group affect the euphoric properties?

I haven't had a chance to taste all that many 'exotic' benzos, mostly just val, xan, clon and ativan, so I don't have the portfolio JasonCrest does, perhaps he can fill in the gaps.

If anyone has tasted (or knows of someone or some study that has) two benzos, the only difference being the 9-halo being substituted for nitro, what is the difference in recreational potential? It seems to me that the most recreational ones tend to have nitro substitutions. Isn't Nimetazepam one of the most abused benzos in the world? Then again, probably one of the more euphoric benzos commonly seen in the US is clonazepam, which also has the 9-nitro grouping instead of a halogen.

Temazepam has the N-methyl group discussed above, but it also has a 3-hydroxy group. Since that's the only thing that makes it stand out (The only other one I've seen with it is lorazepam), I assume that the 3-hydroxy is what gives temazepam it's extra kick.

Based on that, wouldn't this likely be a benzo designed for abuse?

Is this a benzo that already exists? I searched through a couple different vendors, but it's not one I could find.
(Sorry to bring this back from the dead, but I don't think this merits another thread)

 

[mad_scientist]

Many benzos get metabolised by hydroxylation at the 3-position, and the 3-hydroxy analogues are active metabolites.

I'm not sure how the 3-OH group affects activity but it doesn't seem to make them much more potent particularly, my guess is that benzos like temazepam, lorazepam etc that have a 3-OH group were felt to be better drugs because the extra OH had beneficial effects on half-life or solubility.

The drug you have drawn will be an active metabolite of flunitrazepam (rohypnol). It will certainly be active and have high abuse potential, but I doubt its been marketed as a seperate drug. Personally I don't like the 2'-fluoro benzos that much, too much amnesia for my liking, but many people seem to love the increased sedative effects.

 

[Bondmaker]

N-alkylation of benzos....

Kind of, just kind of, reminds me of the "malonyl" substitution of barbiturates. It takes at least a diethyl substitution (veronal) to get weak activity. Holding one C-substituent steady we get more activity as the other C-substituent gets longer or more elaborate until the activity changes from hypnotic to anti-epileptic with substituents greater than 6-carbons long (look at the structures of seconal, nembutal, etc.
It's a stretch of the imagination to even think that N-substituents of benzos have anything in common with C-substituents on the barbiturate skeleton, but ,like, just an idea, eh?

 

[Ham-milton]

Many benzos get metabolised by hydroxylation at the 3-position, and the 3-hydroxy analogues are active metabolites.

I'm not sure how the 3-OH group affects activity but it doesn't seem to make them much more potent particularly, my guess is that benzos like temazepam, lorazepam etc that have a 3-OH group were felt to be better drugs because the extra OH had beneficial effects on half-life or solubility.

The drug you have drawn will be an active metabolite of flunitrazepam (rohypnol). It will certainly be active and have high abuse potential, but I doubt its been marketed as a seperate drug. Personally I don't like the 2'-fluoro benzos that much, too much amnesia for my liking, but many people seem to love the increased sedative effects.

Has anything with a 2-Chloro had much abuse potential? And since a nitro group subs (apparently) better for the halogen @ 8 or 9 position, perhaps it would at sub for the fluoro in Flunitrazepam, too?

 

[mad_scientist]

Yeah lorazepam and clonazepam have a 2'-chloro group, and there are a bunch of others too that I'm less familiar with.

In general with benzos as you move from unsubstituted phenyl --> 2'-chloro --> 2'-fluoro the drug becomes more potent, more sedating, and produces more amnesia.

Chloro and fluoro are the main 2'- substituents that have been used in commercially marketed benzos, but I'm more interested in other substitutions. Using a heterocyclic nitrogen at the 2'-position (i.e. replacing the phenyl ring with 2-pyridyl) as in bromazepam reduces potency quite a bit, but also markedly reduces sedative and amnestic effects while retaining anxiolytic action, which sounds like a profile I'd like, although many people who prefer that messy rohypnol type of buzz dismiss bromazepam as being too weak.

Another unusual substitution pattern is in imidazenil, which has a 2'-bromo and 8-fluoro substitution, and that makes for a very unusual benzo which is a partial agonist at some GABA-a subtypes and an antagonist at others, so a strong anxiolytic and anticonvulsant, yet not only lacks sedative and amnestic effects but actually reverses them when co-administered with more typical benzos.

No idea what a 2'-nitro would do though, my guess is that it might be too bulky and ruin activity entirely, but you never know, it could be a winner...