paroxetine pharmacodynamics (mechanisms/methods of action). What Paxil does and how it does it.
Medicated For Your Protection
I Forgot Why I Cake Topamax
Table of Contents (hide)
When you read about the mechanism of action, or how it works, in Paxil’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.
Pharmacodynamics: The efficacy of paroxetine in the treatment of major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1-, alpha2-, beta-adrenergic-, dopamine (D2)-, 5-HT1-, 5-HT2-, and histamine (H1)-receptors; antagonism of muscarinic, histaminergic, and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs.
Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive.--Paxil PI sheet
as far as we can tell
- Paroxetine is a potent serotonin reuptake inhibitor, the most potent SSRI on the US market. Potency isn’t everything. As Dr. Preskorn wrote:
There is a frequent misconception that potency refers to the dose of a drug needed to produce an effect. That is wrong. Instead, it refers to the concentration of a drug needed to produce an effect. Two drugs may be able to produce exactly the same effect, but the concentration needed of each drug may be quite different. The drug that requires a lower concentration to achieve the same magnitude of effect is the more potent drug regardless of the dose needed to achieve that concentration.--Clinical Pharmacology of SSRIs
- After pure paroxetine gets spiced up with various salts and is converted to paroxetine hydrochloride - Paxil and most generics - or paroxetine mesylate - Pexeva and a few overseas versions - it’s no longer 28 times as potent as fluoxetine. Nevertheless, it still practically floods your brain with serotonin. In some places that’s good, in other places that’s not so good.
- Flooding your brain at the 5-HT1A receptors is good, because too little serotonin there is responsible for things like anxiety, depression, and assorted cognitive problems.
- A little more serotonin at the 5-HT2A if you don’t have enough is good, because that helps regulate sleep. Too much is bad, and when excessive sleep becomes a problem. Too much serotonin at 5-HT2A can also lead to hallucinations and problems caused by too little dopamine.
- A little more serotonin at the 5-HT2C if you don’t have enough is also good for depression and thinking clearly, but too much leads to muddled thinking and weight gain. As with 5-HT2A, you can wind up with even less dopamine, as well as less norepinephrine, which means more cognitive problems, more sleep problems of one kind or another, and more depression.
- And those are just the best-known / most-studied 5-HT receptors, and the ones we know are affected to some degree by serotonergic medications. Extra serotonin at 5-HT1B may be great for aggression and alcoholism, but it’s also another factor in sexual dysfunction2.
- Like Lexapro and Zoloft, Paxil desensitizes 5-HT1A autoreceptors, which is good3.
- Paroxetine is also has a moderate norepinephrine reuptake inhibitor, maybe enough to enhance its antidepressant properties and offset potential side effects, but it’s probably just enough to make the discontinuation syndrome even more hellish.
- Paroxetine is a mild antagonist at some muscarinic receptors. Probably just enough for the anticholinergic side effects that are also side effects of norepinephrine reuptake inhibitors (dry mouth, constipation, urinary retention) to be more likely and worse.
- Which is a feature, not a bug, as far as anyone with IBS is concerned.
- And it might be enough to keep the movement- and hormone-related side effects problems caused by too little dopamine from being worse.
- Finally (they think, so far) paroxetine is a nitric oxide synthase inhibitor, which also contributes to sexual side effects. As if getting too much serotonin at 5-HT1B and messing around with your dopamine weren’t enough to ensure that Paxil will be effective for chemical castration.
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,4 because Lexapro is a derivative of Celexa, a few people will respond differently to the two.
||Keep Crazymeds on the air.
Donate some spare electronic currency
you have floating around The Cloud
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 A deficiency of serotonin at 5-HT1B could be responsible for traits commonly associated with members of college fraternities. That condition makes people prone to aggressive behavior, alcoholism, and, in men, premature ejaculation.
3 Apparently researchers endeavor to obfuscate meaning - with a methodology not dissimilar to medieval guilds - in order to maintain exclusive access to the knowledge within their treatises residing in the public domain.
4 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.
If you have any questions not answered here, please see the Crazymeds Paxil discussion board. We welcome criticisms of the articles, notifications of bad links, site problems, consumer experiences with medications, etc. I’m not always able to write back. Hence I never answer questions about meds via e-mail that are answered by this or other articles. Especially if they have been repeatedly asked on the forum. That’s why we write these damn things. Questions about which meds are best for your condition should also be asked on the forum; because this is a free site, so the price of admission is making things easier for somebody else searching for the same answer. We don’t deal with children on the forum or in private because after doing this for ten years I don’t have the emotional stamina to deal with kids who have brain cooties. How to contact Crazymeds. — Jerod Poore, CME, Publisher Crazymeds (crazymeds.net)
|Last modified on Tuesday, 03 June, 2014 at 13:59:35 by JerodPoore||Page Author Jerod Poore||Date created|
|“Paxil (paroxetine): a Review for the Educated Consumer.” by Jerod Poore is copyright © 2011 Jerod Poore||Published online 2011/04/08|
|Citation options to copy & paste into your article:|
|Plain text:||Poore, Jerod. “Paxil (paroxetine): a Review for the Educated Consumer.” Crazymeds (crazymeds.net). (2011).|
Paxil, and all other drug names on this page and used throughout the site, are a trademark of someone else. Paxil’s PI Sheet will probably have the name of the manufacturer and trademark owner (they’re not always the same company) at or near the very bottom. Or ask Google who the owner is. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of the trademark may have changed without my noticing. It may of changed hands by the time you finished reading this article.
Page design and explanatory material by Jerod Poore, copyright © 2003 - 2015. All rights reserved.
Keep up with Crazymeds and and/or my
slow descent into irreparable madness boring life. Pick your preferred social media target(s):
Follow me for site updates
and research & pharm news.
|Wear my Straitjacket||Batshit Crazy Blog|
Crazymeds | Promote Your Page Too||
Follow for site updates and
high weirdness to distract you.
|Crazymeds’ Tumblr||Crazymeds: The Blog|
Almost all of the material on this site is by Jerod Poore and is copyright © 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, and 2015 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and something along the lines of following disclaimer, I’m usually cool with it.
All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else. Plus we are big pottymouths and talk about S-E-X a lot.
Know your sources!
Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained from the medications’ product information / summary of product characteristic (PI/SPC) sheets and/or medication guides - which is all you get from sites like WebMD, RxList,
NAMBLA NAMI, etc., the sources that are referenced throughout the site, our personal experience and the experiences family, friends, and what people have reported on various reputable sites all over teh intergoogles. As such the information presented here is not intended as a substitute for real medical advice from your real doctor, just a compliment to it. You should never, ever, replace what a real doctor tells you with something from a website on the Internet. The farthest you should ever take it is getting a second opinion from another real doctor. Educate yourself - always read the PI/SPC sheet or medication guide/patient information leaflet (PIL) that comes with your medications and never ever throw them away. OK, you can throw away duplicate copies, but keep at least one, as that’s your proof of purchase of having taken a med in case a doctor doubts your medical history. Plus they take up less space than a bottle, although keeping one inside of a pill bottle is even better.
Crazymeds is not responsible for the content of sites we provide links to. We like them, or they’re paid advertisements, or they’re something else we think you should read to help you make an informed decision about a particular med. Sometimes they’re more than one of those things. But what’s on those sites is their business, not ours.
Crazymeds is optimized for ridiculously large screens and browsers that don’t block ads. I use Firefox and Chrome, running under Windows 72. On a computer that sits on top of my desk. With a 23 inch monitor. Hey, at least you can make the text larger or smaller by clicking on the + or - buttons in the upper right hand corner. If you have Java enabled. Like 99% of the websites on the planet, Crazymeds is hosted on domain running an open source operating system with a variety of open source applications, including the software used to display what you’ve been reading. As such Crazymeds is not responsible for whatever weird shit your browser does or does not do when you read this site3.
No neurologists, psychiatrists, therapists or pharmacists were harmed in the production of this website. Use only as directed. Void where prohibited. Contains nuts. Certain restrictions may apply. All data are subject to availability. Not available on all mobile devices, in the 12 Galaxies Guiltied to a Zegnatronic Rocket Society, or in all dimensions of reality. Hail Xenu!
‘Everything is true, nothing is permitted.’ - Jerod Poore
1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.
2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.
3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?* I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion as anonymity on teh Intergoogles. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.
* Yes, I know I’m using open source browsers. I also test the site using the now-defunct IE and Safari browsers. Their popularity - and superiority - killed IE and Safari, so that’s why I rely on the open source browsers. It’s like brand vs. generic meds. Sometimes the generic is better than the brand.