duloxetine pharmacodynamics (mechanisms/methods of action). What Cymbalta does and how it does it.

Pharmacokinetics & Noted Drug-Drug Interactions | CymbaltaPagesIndex | Comments
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1.  Working Theory

When you read about the mechanism of action, or how it works, in Cymbalta’s PI sheet, it’s almost as vague as how likely it will work. Pretty much every beginning paragraph of the mechanism of action section for every crazy med (and many other non-crazy meds) is a variation on “We don’t know exactly how Panacea, or other drugs like it, works to treat whatever you take it for. In various studies, mostly on rats and other animals, we’ve determined that it does the following…” What you read in the PI sheet is often, but not always the original theorized mechanism of action, or what they thought it does when they started testing the drug for whatever it is now used for1.

After researchers who aren’t being paid by the manufacturer get their hands on med it’s just one study after another, in humans and animals, that supports the original theory. Or determines a precise area in the brain where stuff takes place. Or finds an additional thing the med does. Or finds that it doesn’t do something they originally thought it did. Or finds out that everyone was completely wrong in the first place and the method of action is radically different. That last one does happen. Neurontin (gabapentin) was originally thought to be a synthetic form of GABA that could cross the blood-brain barrier. Turns out that it’s just like every other anticonvulsant and works on voltage channels. Except that it’s unique in that it affects a part of your brain that nothing else touches. Except for Lyrica (pregablin), and a few meds under development (e.g. PD-210714). Still, some people are calling those parts of your brain some people are calling those “gabapentin receptors”, along the lines of benzodiazepine receptors. There supposedly were citalopram receptors as well, but that turned out to be a myth. Ironically gabapentin doesn’t directly affect GABA.

Every day a new peer-reviewed journal is published somewhere adding to our knowledge about how a particular med works, or making us crazier with more contradictory data.

It would be nice if we could break things down into neat parameters like we can with pharmacokinetics, but we can’t. The best we can do is tell you what they originally thought it did, let you know if there are any meds with similar mechanisms / methods (the terms are interchangeable) of action, and give you our best guess as to what it really does based upon more recent research.

2.  How Cymbalta (duloxetine) Works

2.1  What the PI Sheet Says

2.2  What Cymbalta (duloxetine) Really Does

as far as we can tell
Cymbalta is a serotonin and norepinephrine reuptake inhibitor (SNRI). SNRIs boost the amount of serotonin and norepinephrine in various parts of your brain and allow the receptors for those neurotransmitters to marinate longer in them. Neurotransmitter wackiness is a popular theory as to the cause of depression, anxiety, and assorted other brain cooties.

3.  Functional Equivalence

No two medications will have the exact same mechanisms / methods of action. Sometimes a drug that is developed from the active metabolite of another, essentially inert med e.g. Invega (paliperidone) is a predigested form of Risperdal (risperidone) and is basically the same thing. However there is no good conversion of dosages between the two like there is for Tegretol (carbamazepine) and Trileptal (oxacarbazeine). Like Invega and Risperdal, Pristiq (desvenlafaxine) is the active metabolite of Effexor (venlafaxine), but Pristiq has a somewhat different mechanism of action than Effexor. Mainly it kicks Effexor’s ass when it comes to how potent its inhibition of norepinephrine reuptake is.

All SSRIs are essentially interchangeable, making it possible to work out equivalent dosages so you don’t need to wait until you’ve cleared one drug to start another. But Celexa (citalopram) and Lexapro (escitalopram) are vastly more selective than Prozac (fluoxetine), and so the side effect profiles, and pretty much everything else, are very different when you compare Celexa or Lexapro with other SSRIs, but practically identical when compared with each other. While most people couldn’t tell the difference between Lexapro and Celexa,2 because Lexapro is a derivative of Celexa, a few people will respond differently to the two.

3.1  Drugs with Similar Methods of Action as/That Work Like Cymbalta (duloxetine)

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4.  References

  1. Cymbalta (duloxetine) Full US Prescribing Information


Pharmacokinetics & Noted Drug-Drug Interactions | Cymbalta Index | Comments

1 Unlike Lamictal, which was originally thought to be be such a potent folate antagonist that it would work well as a treatment for malaria and similar parasites that took up residence in your brain. Or Topamax, which was originally thought to be an awesome drug for type 2 diabetes, as it looked like it would both control weight and blood sugar.

2 The one real difference used to be cost. Now that Lexapro is available as a generic in the US that difference isn't as great as it once was.


Last modified on Monday, 23 September, 2013 at 02:57:08 by JerodPoorePage Author Date created
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