Tuesday, October 18, 2005

Formulations: theories vs. experience

Strictly from a pharmacological standpoint one might believe that a racemic mixture, half active and half ostensibly inactive, would have identical effect except that one needs twice the concentration of the racemate to procude equal results to the pure active form. For years most experts believed the "pure" form of methadone (almost exclusively used in Germany) was identical to the d/l form used in the rest of the word except it was twice as potent. But it is not so simple - a recent article in Dug Alc Dependence by Verthein and colleagues (2005, vol. 80) suggests there are differences, and withdrawal when switching from one form to the other - though the effects are of a transient nature only


At 8:54 AM, Anonymous Anonymous said...

How curious - particularly as d-methadone appears to have NMDA antagonist properties....One would expect the racemic form to be slightly more potent, no? Of course it's a small study...

-brain hurts-

At 8:00 AM, Anonymous Anonymous said...

dont know - if a compound with some antagnoist properties fgiven together with an agonist, thenpresumably LESS poent - no...?

At 8:58 AM, Anonymous Anonymous said...

Well, I'm probably totally confused.....what seemed like a very simple receptor system 15 years ago just gets more complicated by the day. But I was under the impression that NMDA receptor antagonism (not mu opioid receptor antagonism) reduced tolerance, and therefore produced increased opioid effects. Hence the blending of dextromethorphan with some opioid formulations.

Then in terms of your question, it also seems that the use of VERY small doses of mu opioid antagonists (ie naltrexone) in combination with straight opioid agonists can increase opioid potency. Counterintuitive for sure, but I believe this is because there are EXCITATORY opioid receptors that actually increase pain, and that the naltrexone fills these first but without stimulating them as opioid agonists would. Then the net analgesic effect is reportedly actually increased....

But I may be completely confused....wouldn't be the first time.... ;-)

At 10:48 AM, Blogger RGNewman, MD said...

bottom line: folks differ, meds differ, and folks' reactions to meds differ. Pharmacological theories and wisdom may be powerfully convincing, but opatients react - soemtimes - in unexpected ways. Look at oplacebos: opharmacologically there's ZERO rationale for expecting objective, measurabl;e impact - but that's precisely what one gets, and not uncommonly. So . . . heed the patient.

Vince Dole's story of Szent Gyorgi: nobel laureate with theory that at 0 deg cent muscles can't contract. Watched a frog in his lab get loose and jump into bucket of ice water. Sat there 45 min - and then lo and behold jumped half-way across the room. Vince claimns St. G. at that point soberly assesses the situaiton and concluded: either I am wrong, or the frog is wrong.


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