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Defined by their three-ring chemical structure, almost all tricyclic antidepressants (TCAs) work in pretty much the same way: norepinephrine reuptake inhibition, alpha-1, H1, and M1 antagonism, and sodium voltage channel blocking. Most also do enough serotonin reuptake inhibition to make a difference, and some are also 5HT2A and 5HT2C antagonists. TCAs discussed on this site include:
- Anafranil (clomimpramine)
- dosulepin / dothiepin - Not available in the US
- Elavil (amitriptyline)
- imipramine pamoate
- Norpramin (desipramine)
- Pamelor (nortriptyline)
- Surmontil (trimipramine)
- Tofranil (imipramine)
- Tofranil-PM (imipramine pamoate)
- trimipramine maleate
- Vivactil (protriptyline)
Tetracyclic - having four rings - antidepressants like Remeron and amoxapine are usually lumped in with TCAs even they don’t really work enough like TCAs to warrant that. Enough places and papers refer to Remeron (mirtazapine), etc. as TCAs anyway, so we may as well put them on the same page.1 Although Asendin (amoxapine) is being unofficially classified as an atypical antipsychotic by Stahl and other pharmacologists, based upon its efficacy in treating schizophrenia and mechanism of action.
As far as tricylic ADs are concerned you’d think it would be fairly easy to put together, as there are three essential components of a TCA’s mechanism of action that make it an effective antidepressant: norepinephrine and serotonin reuptake inhibition, and alpha-1 norepinephrine antagonism. Some of them do more, but those are the main three for AD action. Turns out only three are roughly equivalent as far as raw potency is concerned - desipramine, my dear friend protriptyline, and nortriptyline. So while 25mg of desipramine = 25mg of nortriptyline, and it’s close enough to 1:1 until you hit 100mg, protriptyline’s pharmacokinetics are so loopy that I wouldn’t put any money on one 20mg dose of protriptyline being equivalent to two 10mg doses of protriptyline. Then we start getting into some meds being the active metabolites of others and a hell of a lot of other complexities.
Take a look for yourself. These are measures of potency, and potency is not the same as how well a drug works. It isn’t even the same as the effect a drug will have in your brain. Why? These are the base substances, and not the various salts (hydrochloride (HCl), mesylate, pamoate, etc.) that are the active ingredients in many meds. That usually makes a difference in how well a substance is absorbed and distributed throughout your system. According to the results shown on the first table, clomipramine is exactly ten times as potent when it comes to making norepinephrine hang around your synapses than loxapine is, but if the formulations of two drugs resulted in five times as much loxapine per milligram getting to your brain and staying there than was the case with clomipramine, then the clomipramine would be only twice as potent2.
The lower the number, the greater the strength.
SERT: Serotonin transport
NET: Norepinephrine transport
DAT: Dopamine transport
“transport” is another way of referring to reuptake.
These tables are sortable. Just click on a column header to sort the table by that column. Clicking on the same header more than once toggles between ascending and descending.
Binding Profiles of Selected Tricyclic and Tetracyclic Antidepressants
From Tricyclic antidepressant pharmacology and therapeutic drug interactions updated Receptor profile, Ki (nmol/l), of TCAs and comparator drugs: uptake inhibition and receptor antagonism (HCR data)
Mixed with the NSRI reboxetine for comparison.
If you like these kind of data, see the page on SSRI dosage equivalents.
2 I made that up just to have an example using TCAs. A real case is Paxil vs. Prozac. Paroxetine is 14 times as potent as fluoxetine in serotonin reuptake inhibition, but Paxil (paroxetine HCl) is only twice as potent as Prozac (fluoxetine HCl).
Tricyclic & Tetracyclic Antidepressants (TCAs) by Jerod Poore is copyright © 2011
Author: Jerod Poore. Date created: 26 November 2010 Last edited by: JerodPoore on: September 05, 2013, at 05:27 PM
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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?
[begin rant] I rent a dedicated server for Crazy Meds. It’s sitting on a rack somewhere in Southern California along with a bunch of other servers that other people have rented. The hardware is identical, but no two machines have exactly the same operating systems. I don’t even need to see what is on any of the others to know this. If somebody got their server at the exact same time, with the exact same features as I did, I’m confident that there would be noticeable differences in some aspects of the operating systems. So what does this mean? For one thing it means that no two computers in the same office of a single company have the same operating system, and the techs can spend hours figuring out what the fuck the problem could be based on that alone. It also means that application software like IP board that runs the forum here has to have so many fucking user-configurable bells and whistles that even when I read the manual I can’t find every setting, or every location that every flag needs to be set in order for a feature to run the way I want it to run. And in the real world it means you can get an MBA not only with an emphasis on resource planning, but with an emphasis on using SAP - a piece of software so complex there are now college programs on how to use it. You might think, “But don’t people learn how to use Photoshop or Adobe Illustrator in college?” Sure, in order to create stuff. And in a way you’re creating stuff with SAP. But do you get a Bachelor of Fine Arts degree with an emphasis on Photoshop?
Back in the Big Iron Age the operating systems were proprietary, and every computer that took up an entire room with a raised floor and HVAC system, and had less storage and processing power than an iPhone, had the same operating system as every other one, give or take a release level. But when a company bought application software like SAP, they also got the source code, which was usually documented and written in a way to make it easy to modify the hell out of it. Why? Because accounting principles may be the same the world over, and tax laws the same across each country and state, but no two companies have the same format for their reports, invoices, purchase orders and so forth. Standards existed and were universally ignored. If something went wrong it went wrong the same way for everyone, and was easy to track down. People didn’t need to take a college course to learn how to use a piece of software.
I’m not against the open source concept entirely. Back then all the programmers read the same magazines, so we all had the same homebrew utilities. We even had a forerunner of QR Code to scan the longer source code. Software vendors and computer manufacturers sponsored conventions so we could, among other things, swap recipes for such add-ons and utilities. While those things would make our lives easier, they had nothing to do with critical functions of the operating system. Unless badly implemented they would rarely cause key application software to crash and burn. Whereas today, with open source everything, who the hell knows what could be responsible some part of a system failing. [/end rant]
Author: Jerod Poore Date Modified: 2013–12–04 Date Published: 2010–11–26