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Dr. Bob is Robert Hsiung, MD,
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Posted by med-amorphosis on May 20, 2010, at 18:36:21
In reply to Re: Gone with trimipramine, posted by med-amorphosis on May 18, 2010, at 11:17:37
> * Strong: 5-HT2, mACh, H1, H2, α1-adrenergic
> * Moderate: D2
> * Weak: 5-HT1, α2-adrenergic
> Can anyone help explain these actions for me? Much appreciated!!!OOps! copy & paste didn't quite work there!
Posted by bulldog2 on May 20, 2010, at 18:36:21
In reply to Gone with trimipramine, posted by med-amorphosis on May 18, 2010, at 11:13:10
> Surprisingly, my pdoc's first suggestion was to add bupropion the the mixture, keeping the lofepramine too. But I opted for a switch in TCAs 1st. He was willing to try 3 TCAs starting with trimipramine (Surmontil). If that fails then amitryptyline and finally, imipramine. Although imipramine would be used after various other options have been tried- ie a last resort.
>
> So im swapping 210mg/day lofepramine to 25mg trimipramine, slowly titrating to 100mg at week 3.
>
> Any trimipramine experiences anyone would like to share? Any knowledgable babblers explain how its meant to work? Apart from re-uptake inhibition the remainder of its actions slightly baffle me in this description:
> http://en.wikipedia.org/wiki/Trimipramine
> maybe its not the best source. Can anyone explain its effects in plain english (or there abouts)?
>
> medFrankly sounds like more of a sedative than an antidepressive.
Posted by linkadge on May 20, 2010, at 18:36:21
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 13:36:54
Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
After all, its this flawed logic that produces the so called "tianeptine paradox"
Linkadge
Posted by SLS on May 20, 2010, at 18:36:22
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 14:16:35
Hi Linkadge.
> Trimipramine has the same opioid like effects as other TCA's.
Can you elaborate on this? I really don't know that much about it. Does it produces DA release?
I read a recent bulletin that reported the isolation of a genetic variant of the mu opioid receptor that is contributory to alcoholism. It is supposed to produce a greater release of dopamine. I posted it on the Substance Use board.
- Scott
Posted by ed_uk2010 on May 20, 2010, at 18:36:22
In reply to Gone with trimipramine, posted by med-amorphosis on May 18, 2010, at 11:13:10
> Surprisingly, my pdoc's first suggestion was to add bupropion the the mixture, keeping the lofepramine too. But I opted for a switch in TCAs 1st. He was willing to try 3 TCAs starting with trimipramine (Surmontil). If that fails then amitryptyline and finally, imipramine.
I wouldn't expect trimipramine to produce any serious interactions with isocarboxazid. It sounds like a reasonable choice.
Trimipramine is quite sedating. It is particularly suitable for depression with insomnia.
Posted by bulldog2 on May 20, 2010, at 18:36:22
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 14:16:35
> Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
>
> Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
>
> I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
>
> After all, its this flawed logic that produces the so called "tianeptine paradox"
>
>
> LinkadgeYes it is possible it might have ad properties. There also was someing wikipedia that inidcated it might have strong neuropletic properties.
Posted by linkadge on May 20, 2010, at 18:36:22
In reply to Re: Gone with trimipramine » linkadge, posted by SLS on May 18, 2010, at 14:35:55
The TCA's antidepressant effect is (at least partly) due to interaction with opioid receptors. The TCA's display delta agonist like effects, as well as interaction with kappa receptors.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:22
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 17:38:26
>Yes it is possible it might have ad properties. >There also was someing wikipedia that inidcated >it might have strong neuropletic properties
It does have AD properties, thats why it is marketed as an antidepressant. It only has moderate d2 antagonism compared to 5-ht2 antagonism, so the neuroleptic like effects are not strongly pronounced till high doses.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 17:38:26
keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
Linkadge
Posted by Bob on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:30:50
> The TCA's antidepressant effect is (at least partly) due to interaction with opioid receptors. The TCA's display delta agonist like effects, as well as interaction with kappa receptors.
>
> Linkadge
Would any of those actions at opioid, kappa, or delta receptors have anything to do with their putative pain relieving attributes? From most of the reading I've done (and from what my doctor says) the anti-pain properties come from the presence of dual action on serotonin and norepinephrine only. I'm taking nortriptyline now, but it doesn't seem to reduce pain much.
Posted by Bob on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:35:58
> keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
>
>
> Linkadge
From what I understand, Mianserin has been largely superceded by mirtazapine so I guess that would explain why it doesn't seem to be prescribed as an AD these days, but why is it no one is using ritanserin?
Posted by SLS on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:30:50
> The TCA's antidepressant effect is (at least partly) due to interaction with opioid receptors. The TCA's display delta agonist like effects, as well as interaction with kappa receptors.
>
> LinkadgeThank you very much for the info. I was able to come up with a recent abstract on Medline based upon what you said. I imagine you have seen it already, but just in case you haven't, here is the URL:
http://www.ncbi.nlm.nih.gov/pubmed/19828880
Doesn't kappa stimulation produce dysphoria?
- Scott
Posted by SLS on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:35:58
> keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
I might be wrong, but I think ritanserin by itself is not so effective as an antidepressant, although it might make a good augmenter. I doubt that we will ever see it marketed, though. As monotherapy, I don't think there are any indications that it would be appropriate for. I'm all but sure that the patent has expired, and no drug company would want to develop it. As a (non-selective) 5-HT2 receptor antagonist, it might even be effective in treating the negative symptoms of schizophrenia, but would not be a sufficient treatment for the entire symptom cluster.
- Scott
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by ed_uk2010 on May 18, 2010, at 15:44:06
> I wouldn't expect trimipramine to produce any serious interactions with isocarboxazid. It sounds like a reasonable choice.
>
> Trimipramine is quite sedating. It is particularly suitable for depression with insomnia.Well after my 1st night at 50mg (my appologies, but im desperate. Im not encouraging others to self increase dosage) and I awoke earlier than I have for a long long time. I was asleep by 12:30 and up at 9. Thats good for me. I expected to wake feeling hung over from starting trimipramine, especially as I combining with clonazepam. But I felt refreshed if anything. Nothing like clomipramine (yuck!-SSRI-in-disguise) Yes trimipramine knocks you out but sleep isn't foggy-I vaguely remembered dreams on waking. I hardly ever dream, unless they're nightmares.
I also must remember that there is still lofepramine in my system. That needs to be rid of before I can make any trully acurate reports.
Anyone know how long it takes 'till there is neg amounts in the blood and/or lofepramine's NRI effect diminishes?
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 17:38:26
> > Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
> >
> > Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
> >
> > I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
> >
> > After all, its this flawed logic that produces the so called "tianeptine paradox"
> >
> >
> > Linkadge
>
> Yes it is possible it might have ad properties. There also was someing wikipedia that inidcated it might have strong neuropletic properties.Well I can say that the Surmontil brand is ONLY marketed as an AD here, or with associated anxiety. How can you question its AD abilities when its been used and marketed as such for so long?
Posted by hyperfocus on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine » ed_uk2010, posted by med-amorphosis on May 19, 2010, at 14:10:15
I also have this kind of paradoxical sleep, but with amitriptyline. Many days I sleep less and wake up more refreshed, much better than when I fall asleep with benzos or Risperdal. A few times I woke up after three or four hours feeling great physically. Maybe TCAs promote more REM sleep? Sleep on benzos feels shallow.
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by hyperfocus on May 19, 2010, at 15:22:08
> I also have this kind of paradoxical sleep, but with amitriptyline. Many days I sleep less and wake up more refreshed, much better than when I fall asleep with benzos or Risperdal. A few times I woke up after three or four hours feeling great physically. Maybe TCAs promote more REM sleep? Sleep on benzos feels shallow.
Yeah its odd. I took 25mg 2hrs ago before dinner. I'm still up, feel slightly sedated, very calm yet not at all drowsy. Yet if I laid down I know I could fall asleep. I also had a strange energizing effect after waking after my 1st dose taken at 8pm last night. I woke just after 9pm, went online, listened to some musice then took another 25mg before midnight. I was asleep shortly after. NO 'doziness' at all yet.
Posted by bulldog2 on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine » bulldog2, posted by med-amorphosis on May 19, 2010, at 14:16:47
> > > Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
> > >
> > > Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
> > >
> > > I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
> > >
> > > After all, its this flawed logic that produces the so called "tianeptine paradox"
> > >
> > >
> > > Linkadge
> >
> > Yes it is possible it might have ad properties. There also was someing wikipedia that inidcated it might have strong neuropletic properties.
>
> Well I can say that the Surmontil brand is ONLY marketed as an AD here, or with associated anxiety. How can you question its AD abilities when its been used and marketed as such for so long?I think my point has been misunderstood. This med might be a wonderful ad. I however was reading in wikipedia about this med being tested on 28 people as a neuropletic med and it seems to have done a good job. Read the wikipedia article about surmontil and it is in the bottom half. This might be a good ad for someone with anxiety issues. Kill two birds with one stone.
Posted by SLS on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 19, 2010, at 16:13:14
> I think my point has been misunderstood. This med might be a wonderful ad. I however was reading in wikipedia about this med being tested on 28 people as a neuropletic med and it seems to have done a good job. Read the wikipedia article about surmontil and it is in the bottom half. This might be a good ad for someone with anxiety issues. Kill two birds with one stone.
Amoxapine (Asendin) is a tricyclic with moderate neuroleptic properties. It is a relative of loxapine. It was thought that this drug, too, could serve a dual purpose. It never became popular, even though it was touted as working faster than other TCAs to treat depression.
- Scott
Posted by linkadge on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine » linkadge, posted by SLS on May 19, 2010, at 7:16:52
Kappa stimulation can produce acute dysphoria, but long term adminitration may reduce the responsivity of the kappa receptors to dynorphin.
Kappa receptor agonists might also have analgesic and mood stabilizing effects.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine, posted by SLS on May 19, 2010, at 7:27:00
Ritanserin was/is an effective antidepressant (as effective as any) from the abstracts I have read. I also read that ritanserin inhibits dopamine reuptake. See:
http://www.nature.com/mp/journal/v5/n6/full/4000804a.html
Similar effectiveness to amitriptyline:
http://www.biopsychiatry.com/ritanserinvamitrip.htm
I think there is still this assumption that just because it is not a serotonin/norepinephrine reuptake inhibitor, it is not an effective antideressant.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine » bulldog2, posted by med-amorphosis on May 19, 2010, at 14:16:47
Think of it this way: Surmontil could have potent dopaminergic effects on account of
1) 5-ht2a/c receptor antagonism
2) Muscarinic antagonism
3) MAO-B inhibition
4) DAT inhibition
5) 5-ht2a/c antagonism
6) Opioid bindingYes it does have some d2 antagonsm, but this would indirectly shunt more dopamine to d1/d3 etc.
Linkadge
Posted by SLS on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by linkadge on May 19, 2010, at 18:16:00
> I think there is still this assumption that just because it is not a serotonin/norepinephrine reuptake inhibitor, it is not an effective antideressant.
I can only hope that this is not true of our scientists.
As far as ritanserin is concerned, I am not convinced that it is as effective as the other drugs that we use for depression. I think if it were really that effective, more placebo controlled trials of its use in depression would have been published. I don't think I have come across a single study that looked at ritanserin as a treatment for major depressive disorder as diagnosed using DSM criteria. For now, I guess it ia a moot point. I don't think we will see it any time soon.
- Scott
Posted by linkadge on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by SLS on May 19, 2010, at 18:55:40
I don't see any reason why it would be less effective. Ritanserin was more of a research drug, true, but without evidence to suggest that it is inferior, I don't see why I would conclude so.
The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
Linkadge
Posted by SLS on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by linkadge on May 19, 2010, at 20:10:49
> I don't see any reason why it would be less effective.
However, it is so few times that we can yet predict the therapeutic value of a drug based upon what we think we know. Strattera and reboxetine suck for depression, yet they had the "right" properties to be effective according to what are probably outdated and impotent theories.
It seems that we have two head-to-head comparisons of ritanserin to another drug for treating depression. There is the one you cited that speaks of depression without stating the use of DSM criteria, and another for a DSM diagnosis of dysthymia. In the latter study, ritanserin was found to be inferior to imipramine. I don't know how relevant this is, though, as dysthymia is a different disorder than major depressive disorder. The former study fails to describe the relative potencies of its two test drugs. One thing seems clear. Ritanserin has not been thoroughly evaluated for treating major depression. You may be right about ritanserin.
> The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
You sure are right about that. Clorgyline is a prime example. This drug might be the most effective antidepressant yet tested, but it languishes in the laboratory because no one would want to develop a drug without a patent.
- Scott
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