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My psych wants me to start on lofepramine but can someone provide me with more information about this drug and its effectiveness? 

It says it's for major depression but I also have problems with anxiety and I'm afraid this wont help with that as well 

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If it says SERT is 70 and NET is 5.4 are there any SSRIs that have similar mechanisms of actions? Is SERT 70 a weak inhibitor of Serotonin?

 

Could someone explain at what doses Serotonin is inhibited or what doses a good amount of serotonin is inhibited? 

I realise this drug has a higher favourability for Norepinephrine but does it work like Venlafaxine? Where in this case serotonin is only inhibited at a certain dose and at a certain dose the maximum amount of serotonin can be inhibited?

What is really the maximum amount of serotonin that is inhibited? Sorry I'm so stupid and confused. 

Sertraline is the most potent serotonin inhibitor and it inhibits serotonin by 2.8 (the lower the number the more potent) and the NET is 925 and DAT is 315 

so many people say at the higher doses of Sertraline they experience the Dopamine and Norepinephrine action and it makes them a bit 'manic' so in light of this does this mean that only at higher doses of lofepramine will I experience serotonin effects? 

And furthermore it says it is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors (Ki values of 67 nM, 330 nM, 130 nM, 340 nM, 460 nM for M1, M2, M3, M4 &M5 respectively). What significance does this have with depression?

Escitalopram is the most specific serotonin inhibitor SERT is 2.5 and NET is 6541 so of course you will not get any norepinephrine action on any dose of Escitalopram

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I don't know much about tricyclics and even less about lofepramine but the majority of tricyclics were replaced by SSRIs, SNRIs and NRIs. Tricyclics are sometimes referred as "dirty antidepressants" because these affect other parts of the brain's functioning which isn't necessarily the purpose of its use with today's drugs such as SSRIs and SNRIs which target specific parts of the brain. So they get used off label a lot of the time for other purposes such as pain management. On top of preventing the reuptake inhibition of serotonin it also works a potent antihistamine and anticholinergic which is beneficial in tackling comorbid anxiety as it provides a sedating effect. So it should provide relief for your anxiety.

 

Just to educate a little, I don't know if you fully understand the purpose of antidepressants from your post don't, they don't inhibit serotonin, quite the opposite in fact. They prevent the reuptaking of serotonin. Think of them as a dam on a river, they cause the swelling of serotonin, allowing it to be reused over and over again. And this provides an rise in overall mood.

Edited by Southern Discomfort
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1 hour ago, cryinginmoscow said:

My psych wants me to start on lofepramine but can someone provide me with more information about this drug and its effectiveness? 

It says it's for major depression but I also have problems with anxiety and I'm afraid this wont help with that as well 

Could you talk to your psychiatrist (pdoc) about adding on a kind of anti-anxiety med also? (after trying the lofepramine for a little while?)

Lofepramine's effectiveness is different in everyone.  Sometimes people metabolize it differently, or faster or slower.  People react to different doses in different ways.  It is one of those things that you won't know unless you try it.

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I took lofepramine many years ago, in 1998. It did not help my mood at all.

At lower doses of 70mg and 140mg it had no effect on me and at the higher dose of 210mg I became very irritable and agitated.

 

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46 minutes ago, rowan77 said:

I took lofepramine many years ago, in 1998. It did not help my mood at all.

At lower doses of 70mg and 140mg it had no effect on me and at the higher dose of 210mg I became very irritable and agitated.

 

It has risk of causing mania so it shouldn't be prescribed to bipolar patients I think

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9 hours ago, cryinginmoscow said:

If it says SERT is 70 and NET is 5.4 are there any SSRIs that have similar mechanisms of actions? Is SERT 70 a weak inhibitor of Serotonin?

 

Could someone explain at what doses Serotonin is inhibited or what doses a good amount of serotonin is inhibited? 

I realise this drug has a higher favourability for Norepinephrine but does it work like Venlafaxine? Where in this case serotonin is only inhibited at a certain dose and at a certain dose the maximum amount of serotonin can be inhibited?

What is really the maximum amount of serotonin that is inhibited? Sorry I'm so stupid and confused. 

Sertraline is the most potent serotonin inhibitor and it inhibits serotonin by 2.8 (the lower the number the more potent) and the NET is 925 and DAT is 315 

so many people say at the higher doses of Sertraline they experience the Dopamine and Norepinephrine action and it makes them a bit 'manic' so in light of this does this mean that only at higher doses of lofepramine will I experience serotonin effects? 

And furthermore it says it is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors (Ki values of 67 nM, 330 nM, 130 nM, 340 nM, 460 nM for M1, M2, M3, M4 &M5 respectively). What significance does this have with depression?

Escitalopram is the most specific serotonin inhibitor SERT is 2.5 and NET is 6541 so of course you will not get any norepinephrine action on any dose of Escitalopram

Hey, you're not stupid! Trying to understand psychopharmacology without a medical degree is quite an overwhelming thing to do! It takes a while and lots and lots of reading to gain even a remote understanding of how these meds work. Even then, the more you know, the more you'll feel you don't know (when in fact, you've learned a lot). No need to put yourself down like that.

If the SERT Ki = 70 nM and NET Ki = 5.4 nM, then norepinephrine reuptake inhibition will definitely be much more potent than serotonin reuptake inhibition. 70 nM I believe would be considered a "moderate" potency inhibitor, whereas 5.4 nM would be considered a near "high" potency but not a "very high" potency inhibitor. (One source I read said that "very high" is < 1 nM, "high" is 1-5 nM, "moderate" is 5-100 nM, and weak is > 100 nM. Not sure if that's universal...)

I don't know at what doses serotonin reuptake is inhibited, but I would imagine it would be in the higher dose range, as it looks as though it preferentially inhibits reuptake of norepinephrine.

This drug would work in the opposite way of venlafaxine. Venlafaxine has a higher affinity for the SERT than the NET, a 30:1 ratio of SERT-to-NET with its active metabolite, desvenlafaxine, having a SERT-to-NET ratio of 14:1, whereas lofepramine has a SERT-to-NET ratio of 1:13. In other words, venlafaxine is 30 times more potent a SRI than it is a NRI, desvenlafaxine (Pristiq) is 10 times more potent a SRI than it is a NRI, and lofepramine is 13 times more potent a NRI than it is a SRI. So lower doses of venlafaxine (and Pristiq) exhibit preferential serotonin reuptake inhibition, with higher doses exhibiting simultaneous serotonin and norepinephrine reuptake inhibition (and even higher doses including dopamine reuptake inhibition due to the weak affinity at the DAT), whereas with lofepramine, lower doses will yield primarily norepinephrine reuptake inhibition with higher doses producing simultaneous SNRI actions. Lofepramine, to my knowledge, doesn't have affinity for the DAT, so while you won't get direct dopamine reuptake inhibition, there will be increased dopamine neurotransmission via norepinephrine reuptake inhibition (in the prefrontal cortex), and that happens early on since the NRI actions happen early on.

I read that the affinities for the monoamine transporters of sertraline are 0.21 nM for the SERT, 25.5 for the DAT, and 667 nM for the NET, but that could be wrong. That is true though what you said about sertraline causing some weak dopamine reuptake inhibition at high doses, haven't heard of it causing norepinephrine reuptake inhibition though, that's new to me. 

The weaker the inhibition of muscarinic acetylcholine receptors, generally the better (unless you're taking it for other purposes like extrapyramidal reactions to antipsychotics, tremor, Parkinsonism, hyperhidrosis, etc.). Anticholinergics can produce side effects such as constipation, dry mouth, blurred vision (loss of ability to focus close up, sensitivity to sunlight due to pupil dilation, etc.), memory and cognitive issues, and more. Those are relatively good affinities for a tricyclic antidepressant. For comparison, the average affinity for the mACh (muscarinic acetylcholine) receptors of nortriptyline is Ki = 37 nM, amitriptyline is Ki = 18 nM, doxepin is Ki = 83.3 nM, clomipramine is Ki = 37 nM, imipramine is Ki = 46 nM, desipramine is Ki = 196, trimipramine is Ki = 59 nM, and protriptyline is Ki = 25 nM. The muscarinic acetylcholine receptors being antagonized don't have any interaction as far as I know when it comes to depression though (someone correct me if I'm wrong).

I hope this clarifies things a little for you. :) 

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44 minutes ago, cryinginmoscow said:

It has risk of causing mania so it shouldn't be prescribed to bipolar patients I think

Yes. I wasn't diagnosed with Bipolar until 5 years later. At that point I was diagnosed with MDD and my pdoc  had not picked up on the warning signs.

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