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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by bearfan on August 15, 2010, at 3:53:18
Anyone try one of the RIMAs and know how it compares to a MAOI? I tried Manerix for 2 weeks and got an definite increase in agitation and inability to concentrate due to increased anxiety. My sleep schedule was not much better. Since Moclobermide works on primarily on MAO-A and some MAO-B wouldn't this be similar to Parnate o Nardil or would the they be different?
Posted by SLS on August 15, 2010, at 5:25:15
In reply to RIMAs vs MAOIs, posted by bearfan on August 15, 2010, at 3:53:18
Moclobemide severely exacerbated my bipolar depression. Parnate and Nardil have been of help. Sometimes, you need to discard personal theories and rely on observational evidence. There was insufficient evidence of the effectiveness of moclobemide for the US FDA to approve its use. Anecdotes seem to bear out the fact that MAOI drugs are different enough to be able to justify trials of different drugs despite the clinical failures of one or more.
- Scott
Posted by Tomatheus on August 15, 2010, at 8:55:09
In reply to RIMAs vs MAOIs, posted by bearfan on August 15, 2010, at 3:53:18
Bearfan,
I tried moclobemide and noticed a reduction in some of my depressive symptoms that lasted a few days, but nothing significant after that. Like you, I also noticed some agitation the last time I took the medication. To date, Nardil is the only antidepressant I've taken that's put my depressive symptoms into remission for more than a few days. Goldshield Parnate and enteric-coated Marplan also put my symptoms into remission, but not for more than three days. I also noticed a response from oral selegiline that was weaker than my responses to Nardil, Parnate, and Marplan, and like the latter two medications my response only lasted a few days.
I could be wrong, but my guess is that moclobemide is less effective than Nardil and Parnate because it's reversible, not because it's selective to MAO-A. Selegiline primarily inhibits MAO-B, but begins to exert antidepressant activity at doses that inhibit MAO-A. This, coupled with a study that found clorgyline (an irreversible MAO-A inhibitor) to be a more effective antidepressant than pargyline (an irreversible MAO-B inhibitor), actually supports the notion that MAO-A inhibition is more important than MAO-B inhibition when it comes to the treatment of depression. I personally think that an antidepressant that inhibits MAO-A both selectively and irreversibly would be more effective than any MAOI or RIMA (or possibly even any antidepressant) that's currently available. Unfortunately, no such antidepressant has ever been made available as a prescription antidepressant, as far as I'm aware.
Tomatheus
Posted by SLS on August 15, 2010, at 9:20:27
In reply to Re: RIMAs vs MAOIs, posted by Tomatheus on August 15, 2010, at 8:55:09
> I could be wrong, but my guess is that moclobemide is less effective than Nardil and Parnate because it's reversible, not because it's selective to MAO-A. Selegiline primarily inhibits MAO-B, but begins to exert antidepressant activity at doses that inhibit MAO-A. This, coupled with a study that found clorgyline (an irreversible MAO-A inhibitor) to be a more effective antidepressant than pargyline (an irreversible MAO-B inhibitor), actually supports the notion that MAO-A inhibition is more important than MAO-B inhibition when it comes to the treatment of depression. I personally think that an antidepressant that inhibits MAO-A both selectively and irreversibly would be more effective than any MAOI or RIMA (or possibly even any antidepressant) that's currently available. Unfortunately, no such antidepressant has ever been made available as a prescription antidepressant, as far as I'm aware.
I agree with everything you have written here.
- Scott
Posted by Tomatheus on August 15, 2010, at 10:16:10
In reply to Re: RIMAs vs MAOIs, posted by SLS on August 15, 2010, at 9:20:27
Posted by Phillipa on August 15, 2010, at 10:42:36
In reply to Re: RIMAs vs MAOIs, posted by SLS on August 15, 2010, at 9:20:27
What is a RIMA as when googled it could find no info but one site snd it didn't give any real info. Thanks Phillipa
Posted by Tomatheus on August 15, 2010, at 12:56:09
In reply to Re: RIMAs vs MAOIs, posted by Phillipa on August 15, 2010, at 10:42:36
Phillipa,
A RIMA is a reversible inhibitor of monoamine oxidase A. Unlike irreversible MAO-A inhibitors, RIMAs do not stay bound to MAO-A for the life of the enzyme. Nardil, Parnate, and Marplan are all irreversible MAOIs (which inhibit both types of MAO). Moclobemide and Tririma are examples of RIMAs.
I hope this helps.
Tomatheus
Posted by ed_uk2010 on August 15, 2010, at 14:30:58
In reply to Re: RIMAs vs MAOIs, posted by SLS on August 15, 2010, at 9:20:27
>I personally think that an antidepressant that inhibits MAO-A both selectively and irreversibly would be more effective than any MAOI or RIMA (or possibly even any antidepressant) that's currently available.
Why would a selective & irreversible MAO-A inhibitor be more effective than Nardil/Parnate? I expect that such a drug would be somewhat better tolerated, but probably not more effective.
Posted by SLS on August 15, 2010, at 15:20:28
In reply to Re: RIMAs vs MAOIs » SLS, posted by ed_uk2010 on August 15, 2010, at 14:30:58
> >I personally think that an antidepressant that inhibits MAO-A both selectively and irreversibly would be more effective than any MAOI or RIMA (or possibly even any antidepressant) that's currently available.
>
> Why would a selective & irreversible MAO-A inhibitor be more effective than Nardil/Parnate? I expect that such a drug would be somewhat better tolerated, but probably not more effective.My experience with clorgyline is that it was more effective than Nardil or Parnate at a time when I was totally resistant to everything else. The US NIMH would use clorgyline when all else had failed. It was their opinion that it was the single most effective antidepressant in the world. It is unclear to me as to why it was never developed for marketing, but the patent must surely have expired 20 years ago. There may have been some concern over cardiac side effects. It is interesting, though, that clorgyline has been reported to arrest and even improve congestive heart failure.
- Scott
Posted by ed_uk2010 on August 15, 2010, at 16:06:49
In reply to Re: RIMAs vs MAOIs » ed_uk2010, posted by SLS on August 15, 2010, at 15:20:28
Hi Scott,
>My experience with clorgyline is that it was more effective than Nardil or Parnate at a time when I was totally resistant to everything else.
Do you know whether clorgyline is still available anywhere? Also, what mechanism could explain its possibly superior efficacy? Perhaps it was better tolerated than Nardil or Parnate, and that might allow a particularly high dose to be given.
The new drug TriRima, mentioned above by Tomatheus, sounds quite interesting. Apparently, it is more potent than moclobemide.
Posted by Tomatheus on August 15, 2010, at 16:12:00
In reply to Re: RIMAs vs MAOIs » SLS, posted by ed_uk2010 on August 15, 2010, at 14:30:58
> Why would a selective & irreversible MAO-A inhibitor be more effective than Nardil/Parnate? I expect that such a drug would be somewhat better tolerated, but probably not more effective.
Am I allowed to respond? I don't want to get in the way of your dialogue with Scott, but I think it's only fair that I get to share my thoughts too.
Anyway, I suspect that a selective irreversible MAO-A inhibitor would be more effective than the nonselective irreversible MAOIs currently on the market because elevated levels of MAO-A have been implicated in major depressive disorder, but elevated levels of MAO-B have not. When treating any illness, the goal (in my opinion) should be to target the underlying pathology without creating any unnecessary chemical imbalances. Individuals with high MAO-A levels don't need their MAO-B levels messed with. They simply need their MAO-A levels to be reduced to a healthy, normal level. If MAO-B levels are already at a healthy, normal level, then taking a nonselective MAOI will cause MAO-B levels to drop to a level that's unhealthy. Low platelet MAO (MAO-B) levels have been associated with a subtype of schizophrenia characterized by auditory hallucinations (Schildkraut et al., 1976; Becker & Shaskan, 1977; Orsulak et al., 1978) and even with dysfunctional impulsivity and antisocial behavior (Eensoo et al., 2004). Of course, low MAO-A levels have also been associated with antisocial behavior and aggression, so lowering MAO-A levels too far can also be problematic. My point, though, is that for individuals with high MAO-A levels, it would be far more desirable to simply bring MAO-A levels down to a healthy, normal level without doing anything else than it would be to inhibit MAO-A and to bring MAO-B levels unnecessarily low.
I should point out that what I'm doing is making an educated guess as to whether or not a selective irreversible MAOI would be more effective than the nonselective irreversible MAOIs. There are no studies that I'm aware of that directly compare selective irreversible MAOIs with nonselective irreversible MAOIs, and until there are (which won't be any time soon), all we can really do is make educated guesses.
Tomatheus
==
REFERENCES
Becker, R.E., & Shaskan, E.G. (1977). Platelet monoamine oxidase activity in schizophrenic patients. American Journal of Psychiatry, 134, 512-517. Abstract: http://ajp.psychiatryonline.org/cgi/content/abstract/134/5/512
Eensoo, D., Paaver, M., Pulver, A., Harro, M., & Harro, J. (2004). Low platelet MAO activity associated with high dysfunctional impulsivity and antisocial behavior: Evidence from drunk drivers. Psychopharmacology, 172, 356-358.
Orsulak, P.J., Schildkraut, J.J., Schatzberg, A.F., & Herzog, J.M. (1978). Differences in platelet monoamine oxidase activity in subgroups of schizophrenic and depressive disorders. Biological Psychiatry, 13, 637-647. Abstract: http://psycnet.apa.org/psycinfo/1980-09825-001
Schildkraut, J.J., Herzog, J.M., Orsulak, P.J., Edelman, S.E., Shein, H.M., & Frazier, S.H. (1976). Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients. American Journal of Psychiatry, 133, 438-440. Abstract: http://ajp.psychiatryonline.org/cgi/content/abstract/133/4/438
Posted by emmanuel98 on August 15, 2010, at 20:07:09
In reply to Re: RIMAs vs MAOIs, posted by Tomatheus on August 15, 2010, at 8:55:09
What are RIMAs?
Posted by Tomatheus on August 15, 2010, at 20:24:54
In reply to Re: RIMAs vs MAOIs, posted by emmanuel98 on August 15, 2010, at 20:07:09
> What are RIMAs?
See this post from earlier in the thread:
http://www.dr-bob.org/babble/20100811/msgs/958684.html
Tomatheus
Posted by Phillipa on August 15, 2010, at 20:25:47
In reply to Re: RIMAs vs MAOIs, posted by emmanuel98 on August 15, 2010, at 20:07:09
I had the same qestion and Tomes sp? explained it well. And thanks and sorry for not remembering your name spelling. That is rude of me. Phillipa
Posted by Tomatheus on August 15, 2010, at 20:33:42
In reply to Re: RIMAs vs MAOIs » emmanuel98, posted by Phillipa on August 15, 2010, at 20:25:47
> I had the same qestion and Tomes sp? explained it well. And thanks
You're welcome.
> and sorry for not remembering your name spelling. That is rude of me. Phillipa
Don't worry about it. My user name is difficult to spell.
Tomatheus
Posted by SLS on August 16, 2010, at 5:36:08
In reply to Re: RIMAs vs MAOIs » SLS, posted by ed_uk2010 on August 15, 2010, at 16:06:49
> Hi Scott,
>
> >My experience with clorgyline is that it was more effective than Nardil or Parnate at a time when I was totally resistant to everything else.
>
> Do you know whether clorgyline is still available anywhere?It is no longer available anywhere for human consumption. It is used today as the standard ligand for assaying MAO-A activity in the lab.
> Also, what mechanism could explain its possibly superior efficacy?
I really don't know. Perhaps MAO-B inhibition is somehow counterproductive. I don't think it is unreasonable to categorize MAO-A as the enzyme of depression and MAOI-B as the enzyme of Parkinsonism. Several older studies found that MAO-A will actually metabolize dopamine in certain brain regions. At least one newer study contradicts this, though.
> Perhaps it was better tolerated than Nardil or Parnate, and that might allow a particularly high dose to be given.
Clorgyline is a potent drug. 5-10mg will often be all that is necessary to elicit an antidepressant response. I found it to be quite tolerable at 15mg. Dosages of 30mg of clorgyline had been used on children to investigate its utility in ADD/ADHD. My guess is that increased tolerability is not a factor in the superior therapeutic properties of clorgyline.
> The new drug TriRima, mentioned above by Tomatheus, sounds quite interesting. Apparently, it is more potent than moclobemide.
Wow. I would try it.
> http://www.cenerx.com/Products/rima-data.html
Thanks for the link.
- Scott
Posted by ed_uk2010 on August 16, 2010, at 15:50:14
In reply to Re: RIMAs vs MAOIs » ed_uk2010, posted by Tomatheus on August 15, 2010, at 16:12:00
>Am I allowed to respond?
Yes, of course. Why would you think that you might not be allowed to?!
You make some excellent points. Now about moclobemide... I've been wondering whether the problem with moclobemide is not its reversibility, but its very short duration of action. It has an extremely short half life and I suspect that it does not consistently inhibit MAO-A across day, despite twice a day dosing. On average, moclobemide's half-life is about 3 hours. In some patients, it is as little as 2 hours. For a *reversible* inhibitor of MAO, how can this be adequate?
I wonder whether moclobemide would be more effective if given more frequently? 150mg four times a day might work.
Posted by ed_uk2010 on August 16, 2010, at 15:54:28
In reply to Re: RIMAs vs MAOIs, posted by SLS on August 16, 2010, at 5:36:08
>Wow. I would try it.
I'm always interested in the possibility of new MAOIs. We already have quite enough SSRIs!
Also, see my above post about moclobemide. I wonder whether it worsened your depression because your monoamine levels were going 'up and down' throughout the day. This seems inevitable if it's only given twice a day as per the manufacturer's intructions. I think this might be counterproductive. Do you agree that more frequent administration might allow it to be effective?
Posted by SLS on August 16, 2010, at 17:02:23
In reply to Re: RIMAs vs MAOIs » SLS, posted by ed_uk2010 on August 16, 2010, at 15:54:28
> >Wow. I would try it.
>
> I'm always interested in the possibility of new MAOIs. We already have quite enough SSRIs!
>
> Also, see my above post about moclobemide. I wonder whether it worsened your depression because your monoamine levels were going 'up and down' throughout the day. This seems inevitable if it's only given twice a day as per the manufacturer's intructions. I think this might be counterproductive. Do you agree that more frequent administration might allow it to be effective?Perhaps, generally. However, the hideousness of my reaction to moclobemide was an exacerbation of depression rather than a benign lack of effect. I think I understand your idea regarding an oscillation of MAO inhibition occurring around dosing. I don't know if my experience can be attributed to that. It's a good idea, though.
- Scott
Posted by Tomatheus on August 16, 2010, at 19:58:39
In reply to Moclobemide issues - very short half-life » Tomatheus, posted by ed_uk2010 on August 16, 2010, at 15:50:14
> You make some excellent points. Now about moclobemide... I've been wondering whether the problem with moclobemide is not its reversibility, but its very short duration of action. It has an extremely short half life and I suspect that it does not consistently inhibit MAO-A across day, despite twice a day dosing. On average, moclobemide's half-life is about 3 hours. In some patients, it is as little as 2 hours. For a *reversible* inhibitor of MAO, how can this be adequate?
>
> I wonder whether moclobemide would be more effective if given more frequently? 150mg four times a day might work.Ed,
You could be right about moclobemide's efficacy problem having to do with its short half-life. I'm pretty sure that I tried taking it three times a day at one point, but I'm not sure if I ever went up to 150 mg four times daily. I agree that such a dose might increase the medication's effectiveness.
Tomatheus
Posted by sigismund on August 18, 2010, at 0:15:10
In reply to Re: RIMAs vs MAOIs » ed_uk2010, posted by SLS on August 16, 2010, at 17:02:23
IIRC, Scott, you found moclobemide cripplingly anxiogenic.
I suppose there's no reason to say that that is not depression?
Posted by SLS on August 18, 2010, at 4:55:04
In reply to Re: RIMAs vs MAOIs » SLS, posted by sigismund on August 18, 2010, at 0:15:10
> IIRC, Scott, you found moclobemide cripplingly anxiogenic.
>
> I suppose there's no reason to say that that is not depression?My reaction to moclobemide was an exacerbation of depression in the absence of anxiety. It was hell.
- Scott
Posted by ed_uk2010 on August 18, 2010, at 16:48:48
In reply to Re: RIMAs vs MAOIs » sigismund, posted by SLS on August 18, 2010, at 4:55:04
>My reaction to moclobemide was an exacerbation of depression in the absence of anxiety.
Strange. Why would it do that? You don't think the exacerbation was due to withdrawal from your previous med?
Posted by bearfan on August 19, 2010, at 20:28:48
In reply to Re: RIMAs vs MAOIs » SLS, posted by ed_uk2010 on August 18, 2010, at 16:48:48
I read somewhere that Moclobermide doesn't deactivate MAO nearly as effective as other MAOIs. The new RIMA in development (Tyrima) said it is 100x more efficient in dealing with this than Moclobermide.
This is the end of the thread.
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