Can anyone understand "Binding profiles" of Meds?

[Blahblah]

Researching TCA's because it may be something I will bring up to pdoc. I have only tried 1 (Nortryptaline).

Does anyone know how to choose a TCA by the "binding profiles?" Like for example if someone wants something less sedating with little potential for weight gain,  which TCA would be better?

 

[jt07]

Choosing a med based on its binding profiles is not the best way to determine which med is right for you. The best way is to use empirical evidence from studies and experiences of others than to go on the more theoretical territory of binding profiles. Just because something looks good on paper doesn't mean it will work for you. Wellbutrin looks perfect for me "on paper" but it does absolutely nothing to help me. It just makes me worse.

I would say the best way would be to research the meds and make a list to take in to your doctor. Then let your doctor make the final call taking your concerns into account and using his/her knowledge and experience.

My personal experience with tricyclics is that they are all pretty much sedating and all come with the potential of weight gain.

[mikl_pls]

Not all are sedating for me, but all the ones I've tried (except for nortriptyline and protriptyline) have caused weight gain, which doesn't make a very long list. Amitriptyline I only took a small dose of for sleep, so that one doesn't count, but it's a major weight gainer.

Basically the lower the number, the higher the affinity to that receptor, and the higher, the lower, etc.

So if you want to avoid sedation and weight gain, look for ones with high H1 and potentially 5-HT2C values.

I don't know where you live so I don't know what antidepressants are available, so I'll be all-inclusive.

Concerning the H1 histamine receptor (skipping the ?'s) (bold are TCAs)

1. Venlafaxine >35000
2. Nefazodone 24000
3. Sertraline 24000
4. Paroxetine 22000 (but this med is commonly said to be sedating)
5. Fluvoxamine >10000 (this med was sedating to me)
6. Bupropion 6700
7. Fluoxetine 6250
8. Atomoxetine 5500 (for ADHD but I've taken as an adjunct antidepressant)
9. Femoxetine 4200 (I don't think this med went through development)
10. Etoperidone 3100 (no longer marketed)
11. Nomifensine 2700 (withdrawn)
12. Duloxetine 2300
13. Escitalopram 1970 (this med sedated me)
14. Mazindol 600 (not available)
15. Citalopram 380 (I've heard this med is sedating)
16. Lofepramine 360 (not available in the US, Canada, Australia, or New Zealand, but available in Ireland, Japan, South Africa, and the UK among other countries)
17. Reboxetine 312
18. Trazodone 220
19. Desipramine 110
20. Protriptyline 60
21. Imipramine 37
22. Clomipramine 31.2
23. Amoxapine 25 (a tetracyclic, but sometimes referred to as a TCA)
24. Nortriptyline 15.1
25. Dosulepin 4
26. Maprotiline 1.7 (a tetracyclic, but sometimes referred to as a TCA)
27. Mianserin 1.0
28. Doxepin 0.24
29. Mirtazapine 0.14

Concerning the serotonin 5-HT2C receptor (skipping the ?'s) (bold are TCAs)

1. Bupropion >35000
2. Paroxetine 19000
3. Venlafaxine >10000
4. Nomifensine >10000
5. Fluvoxamine 6700
6. Escitalopram 2531
7. Femoxetine 1905
8. Sertraline 1000
9. Atomoxetine 940
10. Duloxetine 916
11. Agomelatine 631
12. Citalopram 617
13. Desipramine 496
14. Reboxetine 457
15. Fluoxetine 255
16. Trazodone 224
17. Buspirone 174
18. Maprotiline 122
19. Imipramine 120
20. Nefazodone 72
21. Clomipramine 64.6
22. Mirtazapine 39
23. Etoperidone 36
24. Doxepin 8.8
25. Nortriptyline 8.5
26. Amitriptyline 6.15
27. Mianserin 2.59
28. Amoxapine 2

I don't know how helpful these lists will be, but I hope they'll help somehow. Good luck in finding the right med for you.

[Iceberg]

Why do you need a TCA specifically? Have you tried most of the SSRIs and SNRIS? That would fit your criteria better of less sedation and possible less weight issue 

[Blahblah]

Thanks @mikl_pls !! This is interesting.

@Iceberg Yes I've literally tried every SSRI and I've tried Cymbalta. I'm honestly terrified of Effexor because of the short half-life. Cymbalta made me crazy when it wore off and I had withdrawal symptoms for months, even after tapering with Prozac. It has a longer half-life than Effexor. I'll admit, sometimes I miss a dose because I travel alot! Keeping this in mind I don't want to get stuck into taking something that could cause a severe breakdown if I only miss 1 dose, or take the med 2 hours later than usual (i get up at all different times in the morning) I need something with smooth coverage.

Edited November 4, 2017 by Blahblah

[browri]

@Blahblah

@mikl_pls is right, a higher number for H1 would mean it's less likely to cause histamine antagonism and less sedation. Another thing to look at is mAch (muscarinic acetylcholine receptors, sometimes also labeled as M1, M2, M3, M4, etc.). Those will contribute to anticholinergic side effects like dry mouth, urinary retention, cognitive side effects, as well as a modest contribution to drowsiness.

If you're concerned about missing doses, also take into consideration the half-life of the medications that you are looking at. The longer the half-life, the more likely you will be able to tolerate missing a dose. This is why Prozac especially is less known for withdrawal side effects.

5HT2C is concerned with satiety, or rather, feeling full and satisfied with a meal. Lower numbers for 5HT2C would mean you would be less likely to be satisfied by a meal and eat more thus contributing to weight gain. 5HT2C blocking can also contribute to weight gain even without increasing the appetite. Antagonism of 5HT2C is one of the reasons Remeron increases the appetite and causes weight gain.

Careful though not to sacrifice positive therapeutic effect in an effort to reduce side effects. You may end up taking a medication that is useless for you. It's important for the binding affinities for the SERT and NET to be strong (low numbers) in order to get the best therapeutic effect. Also consider that the higher the number, the higher the dose you would need to take to have an effect on that receptor. So if you look at desipramine for example, it has an H1 affinity between 60-100, which means that it could potentially have a strong sedative effect, but not like amitriptyline (0.5-1.1) or amoxapine (7.9-25) and you would likely need higher doses to get that effect. Additionally, desipramine is a pretty potent norepinephrine reuptake inhibitor which theoretically would be stimulating and counteract some of the drugs effect on histamine. There's a precarious balance and lots of variables to consider.

[Blahblah]

Thanks @browri for the thoughtful reply. I come across the binding profiles online and I've always wondered how to interpret them (at least on a very basic, amateur level, I'm not a chemistry expert by any means!)

I don't plan choosing a med solely based on its binding profiles, but this is just something I've been intrigued by for awhile. I've been a medication guinea pig for 20 years and with so many to choose from, and so many random trials, I like to be a bit more methodical in choosing: I look at a variety of things. Often I find myself coming here, reading some reviews, trying to figure out the differences between different meds. Then I go to my pdoc feeling a bit more informed to discuss options.

[Wooster]

This is one of the most informative threads I've seen in awhile.

Can we have more psychopharm discussions, please?

 

[browri]

4 hours ago, Wooster said:

This is one of the most informative threads I've seen in awhile.

Can we have more psychopharm discussions, please?

 

I'm always up for a good psychopharm discussion.

[mikl_pls]

Same here.