Methadone isomers and potency

[Canis aureus]

Hey all,

what is that talk of active and inactive isomers, plus superactive levo-isomer methadone. Something bit confusing

 

[Canis aureus]

I'm thinking that: http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/methadone.html

 

[paradoxcycle]

In the case of methadone, it's the levo isomer, not the dextro isomer, that carries the opioid activity (generally true of opioids. Compare: Levo-Dromoran (levorphanol), a highly potent opioid, is the demethylated form of levomethorphan, which is the levo isomer of the non-narcotic antitussive (and, at high doses, dissociative anesthetic/psychedelic) dextromethorphan ("DXM"). In most of the world, the racemate is used, but in Germany, they've always used l-methadone (Polamidon) and have only recently introduced d,l-methadone into clinical use (god knows why).

 

[redeemer]

Well, it says that the methadone isomer levo-methadone is 1.5-2.4 times stronger than racemic methadone, racemic meaning a 1:1 mixture of the levo and dextro isomer).

It's very common for two enantiomers to differ in potency and effects, take Adderall (racemic amphetamine) and Dexedrine (dextro-amphetamine) for example.

 

[Canis aureus]

And that explain how there is apparently lower doses in the use in German, though it is -- or has been -- the levo isomer... interesting!

Maybe the costs of plain active (l isomer) are too high!!!

 

[Canis aureus]

The racemic mixture seems to have some advantages: it (inactive) acts as lowering tolerance, and as anticonvulsant and probably antidepressant (was it NMDA receptor antagonists activity, yes it is).

So, concluding: inactive has active role, so it isn't inactive, LOL.