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1. Three Ring Circus
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:
- amitriptyline HCl
- Anafranil (clomimpramine HCl)
- clomipramine HCl
- desipramine HCl
- dosulepin / dothiepin - Not available in the US
- doxepin HCl
- Elavil (amitriptyline HCl)
- imipramine HCl
- imipramine pamoate
- Norpramin (desipramine HCl)
- nortriptyline HCl
- Pamelor (nortriptyline HCl)
- Surmontil (trimipramine maleate)
- Tofranil (imipramine HCl)
- trimipramine maleate
- Tofranil-PM (imipramine pamoate)
- Vivactil (protriptyline HCl)
2. But Wait, There’s Four
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.
- amoxapine
- Asendin (amoxapine)
- mianserin HCl - Not available in the US
- mirtazapine
- Remeron (mirtazapine)
- setiptiline maleate - Not available in the US
3. TCA Dosage Equivalents
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 HCl, my dear friend protriptyline HCl, and nortriptyline HCl. 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.
3.1 By the Numbers
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
| Med (generic) | SERT | NET | DAT | 5-HT1A | 5-HT2A | α1 | α2 | D2 | H1 | Musc |
|---|---|---|---|---|---|---|---|---|---|---|
| amitriptyline | 4.30 | 35 | 3,250 | 320 | 24 | 26 | 815 | 1,230 | 1.03 | 13.8 |
| clomipramine | 0.28 | 38 | 2,190 | 7,000 | 27 | 38 | 3,200 | 190 | 31 | 37 |
| desipramine | 17.6 | 0.83 | 3,190 | 6,700 | 315 | 115 | 6,350 | 3,400 | 85 | 132 |
| dosulepin | 8.6 | 46 | 5,310 | 2,300 | 258 | 470 | 2,400 | ? | 3.6 | 25 |
| doxepin | 68 | 29.5 | 12,100 | 283 | 26 | 24 | 1,185 | 1,380 | 0.21 | 52 |
| imipramine | 1.40 | 37 | 8,500 | 7,650 | 115 | 61 | 3,150 | 1,310 | 24 | 68 |
| lofepramine | 70 | 5.4 | 18,000 | 4,600 | 200 | 100 | 2,700 | 2,000 | 360 | 67 |
| nortriptyline | 18 | 4.37 | 1,140 | 302 | 43 | 58 | 2,265 | 1,885 | 8.2 | 94 |
| protriptyline | 19.6 | 1.41 | 2,100 | 3,800 | 70 | 130 | 6,600 | 2,300 | 25 | 25 |
| trimipramine | 149 | 2,450 | 3,780 | 8,000 | 32 | 24 | 680 | 180 | 0.27 | 58 |
| amoxapine | 58 | 16.0 | 4,310 | 220 | 0.6 | 50 | 2,600 | 160 | 25 | 1,000 |
| loxapine | 2,400 | 380 | 9,000 | 2,900 | 1.7 | 28 | 2,400 | 70 | 4.9 | 450 |
| maprotiline | 5,800 | 11.1 | 1,000 | 12,000 | 120 | 90 | 9,400 | 350 | 2.0 | 570 |
| mianserin | 4,000 | 101 | 9,400 | 190 | 4.3 | 74 | 4.3 | 2,197 | 1.7 | 820 |
| mirtazapine | >100,000 | 1,640 | >100,000 | ? | 69 | 608 | 19 | >5,454 | 1.6 | 794 |
.
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.
| generic name | 5-HT | NA | H1 | α1 | Musc | 5-HT2A |
|---|---|---|---|---|---|---|
| mirtazapine | >10,000 | 4,600 | 0.14 | 500 | 670 | 16 |
| mianserin | >4,000 | 71 | 0.40 | 34 | 820 | 7 |
| doxepin | 68 | 29.5 | 0.24 | 24 | 83 | 25 |
| amitriptyline | 20 | 50 | 1 | 27 | 18 | 29 |
| imipramine | 7 | 60 | 40 | 32 | 46 | 80 |
| clomipramine | 0.14 | 54 | 15 | 32 | 25 | 35 |
| nortriptyline | 100 | 10 | 6.3 | 55 | 37 | 44 |
| dothiepin | 78 | 70 | 4 | 400 | 38 | 260 |
| desipramine | 18 | 0.83 | 110 | 100 | 100 | 280 |
| reboxetine | 58 | 7.2 | 310 | >1000 | >1000 | >1000 |
.
If you like these kind of data, see the page on SSRI dosage equivalents.
We also have a forum for TCAs on Crazy Meds Talk, and Remeron has its own forum, so if this page and the pages for individual TCAs aren’t enough for you, take a look at that part of this site.
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).
Page created by: Jerod Poore. Date created: 26 November 2010 Last edited by:
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