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Question about (+)- Tramadol & (-)- Tramadol

TheTwighlight

TheTwighlight

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OK, I know much has been said about generics and name-brand drugs and how they are equivalent as far as dosage and effectiveness goes. But recently I had a bottle of Mylan generic tramadol, and Akyma generic tramadol. Neither is outdated, in fact both bottles are new. Here is the weird thing: I swear that the Akyma pills are better than the Mylan. I might be crazy, but I did a little research, and have a question.

As far as tramadol goes, the (+)- enantiomer is 4X more potent than the (-)- enantiomer in terms of mu-opioid and 5-HT binding affinity. The (-)- enantiomer, though, is responsible for the NA reuptake effects. I read that tramadol is a racemic mixture of the two. Is this to say that it is supposed to be an equal mix of the two? (+)- tramadol has a 10-fold higher analgesic effect than (-)- tramadol, so is it possible that a generic company might have an uneven mixture of the two enantiomers, so long as the total dose of tramadol in each pill comes out to 50mg each? This question is regarding the instant release trams.

I know that a lot of people will say that generic or not, they are equal, but I have to take at least 100mg more of the Mylan per day than the Akyma pills to get a roughly equal analgesic effect. Is there something to my theory, or have I lost my fucking mind?
 
But what would explain the difference in effect from the Mylans to the Akymas? I know that I have read that generic have a leeway of up to -20% or +25% as far as dosage goes...is it possible that the Mylans err on the lower side, and the Akymas on the higher? It's not all in my head, I take tramadol every day for FMS pain, and there was a definite difference between the two.
 
It could easily be all in your head; there's no way to know without blind administration. A lot of people have negative feelings about Mylan (at least because of it's terrible fentanyl patch- which even most physicians readily admit is not equal to brand or other generics), so it's feasible that this would extend to other Mylan products and result in a sort of placebo effect.
 
Yes; there is no approved drug with a non-racemic mixture of optical isomers, and as such, all drugs made will be racemic. Not to mention that it's cheaper.
 
Hammilton said:
Yes; there is no approved drug with a non-racemic mixture of optical isomers, and as such, all drugs made will be racemic. Not to mention that it's cheaper.
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straight off the top of my head there is Adderall as an example of non racemic mixture .. there are others.

generics should match the original pharmacopea specs and therefore should be identical, however the generic companies particularly indian ones are notorious for not following their DMF during synthesis and randomly altering the excipients in the formulations.
the point is moot because a lot of the branded drugs now use eastern manufacturers, just with differnt labels on the box
 
Holy_cow said:
Yes, you've lost your fucking mind. The synthesis of tramadol always leads to a 1:1 mixture of the enantiomers.
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not true, the organometallic step is partially enantioselective usually 7:2 ratio between enantiomers
 
vecktor said:
not true, the organometallic step is partially enantioselective usually 7:2 ratio between enantiomers
Click to expand...
No, this is a simple Grignard reaction, and it ALWAYS produces a 1:1 mixture of the stereoisomers. It is diastereoselective, though, and produces a racemic mixture of R, R- and S, S-tramadol, but no R, S- or S, R-tramadol.
 
It does not surprise me that you get different effects! I since long have the feeling that Tramadol is quite variable in regards to its effects in one individual.First I also attributed it to different brands,it might be partially true but it also depends on if you take it with a meal and what kind of meal-stronger with food and again a little stronger with milk (NaHCO3 helps too)etc..Daytime could also matter (where did I see that study about when to take it best?).Pills sometimes appeared more active to me than capsules.

All in all though its a bit erratic and sometimes I get almost no effects from 100mg and the other time I can almost nod off on it once the metabolite has reached its peak.

You know that it has to be converted to an active metabolite (the M1 with its stronger activity at the mu receptor,plus there are many other metabolites) so its no wonder that it can vary.

As a regular user I have tried quite a few brands incl. the Grünenthal original.Its possible to find equal effects with all brands at some times.
 
johanneschimpo said:
This is not true.... why do so many people repeat this??? 8(
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I'm not so sure about that...I was reading a medical book on fibromyalgia in the library, and in the medication part of the book it was talking about this -20%/+25% thing with generics. So where'd they get it from? The book was written by a doctor. Not sure which one it was but I can probably find out.
 
hugo24 said:
It does not surprise me that you get different effects! I since long have the feeling that Tramadol is quite variable in regards to its effects in one individual.First I also attributed it to different brands,it might be partially true but it also depends on if you take it with a meal and what kind of meal-stronger with food and again a little stronger with milk (NaHCO3 helps too)etc..Daytime could also matter (where did I see that study about when to take it best?).Pills sometimes appeared more active to me than capsules.

All in all though its a bit erratic and sometimes I get almost no effects from 100mg and the other time I can almost nod off on it once the metabolite has reached its peak.

You know that it has to be converted to an active metabolite (the M1 with its stronger activity at the mu receptor,plus there are many other metabolites) so its no wonder that it can vary.

As a regular user I have tried quite a few brands incl. the Grünenthal original.Its possible to find equal effects with all brands at some times.
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It's stronger with food, and still moreso with milk? That's cool. I guess eating definitely makes a difference, but I did take that into account before I asked my question. I know about M1, too. Why doesn't a company make O-desmethyltramadol into it's own medication? I guess it would probably be scheduled, though. Still...I bet it's badass by itself.
 
I guessed that you already took food into account,just wanted to re-empasize it because I too focused too much on the brands first before finding out about the relevance of pharmacokinetics and such.Wouldn't still not rule out that the Mylan is worse but I was there before with the Stradols,believe me!

And then,how is this when someone sells a racemate,does he still do a chiral HPLC???And it happens that a crystallization of a nonracemic mixture enriches an enantiomer (or the racemate).

Finally, what works with me (corn flakes with milk etc) might be different in your system.Check out also the influence of pH on absorption and duration.Maybe a slower onset=longer and stronger action?

Only recently I tried Bicarbonate,with good effect part. in duration,but more trials are needed.
 
Posting nonsense is a super way to get banned - nuke
 
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vecktor said:
straight off the top of my head there is Adderall as an example of non racemic mixture .. there are others.

generics should match the original pharmacopea specs and therefore should be identical, however the generic companies particularly indian ones are notorious for not following their DMF during synthesis and randomly altering the excipients in the formulations.
the point is moot because a lot of the branded drugs now use eastern manufacturers, just with differnt labels on the box
Click to expand...

No, what I said wasn't meant to say that there aren't approved drugs that aren't racemic, but rather because the approved Ultram formulation is racemic, the generics will be as well. All US marketed drugs, that is.
 
Hammilton said:
No, what I said wasn't meant to say that there aren't approved drugs that aren't racemic, but rather because the approved Ultram formulation is racemic, the generics will be as well. All US marketed drugs, that is.
Click to expand...

gotcha,
the theory is that a generic should be the same as the branded material, it should always comply with the pharmacopea specification.the gererics should also comply with the description in the drug master file that the FDA have. In reality both branded and generics do vary, the classic is the changing of the source of bulking agents and excipients in tablet formulations which adversely effects absorbtion, one of the versions of old irreversable MAOI's has had problems with this. some generic modafinil seems to have potency/ bioavailability issues compared to the cephalon stuff.
 
Yeah, modafinil is a perfect example of how generics and brands differ. fentanyl patches is another.

If I remember right, because of solubility issues, modafinil tablets don't dissolve nearly as well, and the generics are pretty much worthless. I've never had generic modafinil, though.

There's always been a lot of discussion of the brand and different generic fentanyl patches, and there's a huge difference between Mylan and the other generics and brand. Whereas most, if not all, are gel reservior-type patches, but Mylan has the drug in some sort of adhesive matrix. I'm pretty sure that this was created as an anti-abuse mechanism (I'm pretty sure that's how they got the modified delivery system approved, I read some of the documents filed once).

Do you know which MAOIs? Do you know how it was solved?
 
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