Psycho-Babble Medication Thread 46965

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High doses of Parnate

Posted by Steeler Tookahn on October 21, 2000, at 11:38:47

Has anybody here taken (daily) doses of Parnate over 100 mg? I know the thinking has changed regarding doses of MAOIs and people are using higher doses. I'm at 90 now and am wondering how high I can go. Has anyone gotten more benefits from higher doses?

 

Re: High doses of Parnate

Posted by Sharon J. on October 21, 2000, at 14:47:06

In reply to High doses of Parnate, posted by Steeler Tookahn on October 21, 2000, at 11:38:47

Hi. I was on Parnate for 9 years, and got to taking 80 mg one day, and 90 mg the next, alternatively, and I found it was excellent. At this time, my depression is in remission, and I do not take any anti-depressant (with Dr.'s guidance), but would not hesitate in a moment to go back to taking it if I needed to if it weren't for the new information that I learned after getting off it. I'm sure you know about the food restrictions and drug interactions, but the real down side of taking it for me is all the risks and complications that could arise should I ever have a medical emergency or accident where I would need anesthesia -- I learned from my new Doc that MAOIs don't mix with anesthesia, and I know that if I am severely hurt in a wreck or something and need immediate surgery to save my life, the idea of having to wait until Parnate is washed out completely (and at those dosages can be a long time -- weeks!) before I can have anesthesia and get emergency surgery is not something that I am willing do. Period. I probably gave more info than you asked for, but those are the pluses and minuses that I put in priority with regards to my taking Parnate. It was great for my depression at high doses, but I will search for a different med to take when I need an antidepressant in the future. There is something called a 'reversible' MAOI that is supposedly not as risky for my overall health with regards to drug interactions, and I will most likely consider that alternative when the time comes. If any "professional" has information that will fine-tune what I have said here or correct any misstatements that I have made, I am sure that they will do so. Good luck.

 

Re: High doses of Parnate

Posted by Steeler Tookahn on October 21, 2000, at 15:34:44

In reply to Re: High doses of Parnate, posted by Sharon J. on October 21, 2000, at 14:47:06

Sharon,
Thanks. That was not too much information. I welcome all info. I'm aware of the potential problems with anesthesia but that's the least of my concerns right now. I can understand why that that would make you leery though.
I'm returning to Parnate after having been off it for 2 years. It worked great for me in the past but required higher and higher dosages over a 7 year period. My body seems to be "adapting" to the Parnate too quickly this time. I know that Parnate will be effective for me when I get a certain set of reactions approx. 1 hour after taking it: elevated temperature, nervousness, slight dip in BP. After a week of taking it with these (mild to me) side effects I usually start to get the antidepressant effect (with nasty insomnia). Now I take 5 pills in the morning and barely feel it, and the 4 pills in the afternoon I don't feel at all.
I'm wondering if taking more at one time would make a difference. I'm also wondering how high I can up the dosage (with doctor's supervision, of course). Any input would be appreciated.

 

Re: High doses of Parnate Steeler Tookahn

Posted by Sharon J. on October 21, 2000, at 16:05:13

In reply to Re: High doses of Parnate, posted by Steeler Tookahn on October 21, 2000, at 15:34:44

Steeler:

Glad I didn't "dump" too much info. It is so interesting for me to read of how much awareness you have as to your body responses to Parnate. I knew I "felt" different things, but never pinpointed it so precisely as you.

I hope someone picks up on this thread that can give you input about going higher than 90 mg.

I'll keep an eye on this thread to see what I can learn from what others offer.

Best to you!

 

Re: High doses of Parnate

Posted by SLS on October 21, 2000, at 18:30:50

In reply to High doses of Parnate, posted by Steeler Tookahn on October 21, 2000, at 11:38:47

Hi Steeler.

I have taken as much as 150mg of Parnate in combination with 300mg of imipramine. I have also taken Parnate 120mg + desipramine 200mg + Dexedrine 15mg + T4 thyroid. While already taking Parnate 120mg, I have added nortriptyline, imipramine, and Wellbutrin seperately.

I think you will be able to get a good feel for how safe and effective the high-dosage Parnate strategy can be by referring to Dr. Bob's Psychopharmacology Tips.

I have come across some research studies that indicate that Parnate begins to do things at high dosages that it does not do at lower dosages that are unrelated to MAO inhibition. One such effect is the downregulation of 5-HT2 receptors, something that occurs with several other antidepressants. Unlike Nardil, Parnate has been shown to produce a decrease in dopamine D2 receptor densities.

Jay Amsterdam, MD, has used high-dosage Parnate treatment for difficult cases for at least 10 years. Some people have needed as much as 300mg per day.

Good luck.


- Scott

 

Re: High doses of Parnate

Posted by Steeler Tookahn on October 22, 2000, at 8:45:37

In reply to Re: High doses of Parnate, posted by SLS on October 21, 2000, at 18:30:50

Thanks very much Scott,
I'm glad to get an idea of the kind of doses people are using these days. I read Jay Amsterdam's paper on high doses of Parnate.
I'm also glad to see people using TCAs with MAOIs. I've tried practically everything as an adjunct with little success. A tri-cyclic may be in the future.

>I have come across some research studies that indicate that Parnate begins to do things at high dosages that it does not do at lower dosages that are unrelated to MAO inhibition. One such effect is the downregulation of 5-HT2 receptors, something that occurs with several other antidepressants. Unlike Nardil, Parnate has been shown to produce a decrease in dopamine D2 receptor densities.

Scott -could you elaborate on what this downregualtion might mean to the patient. My knowledge of neurobiology (as well as my Neurobiology itself) is not what it used to be. I don't think I could tell an Axon from a Dendrite without a microscope (that's an attempt at humor).

 

Re: High doses of Parnate Steeler Tookahn

Posted by SLS on October 22, 2000, at 11:19:16

In reply to Re: High doses of Parnate, posted by Steeler Tookahn on October 22, 2000, at 8:45:37

Dear Steeler,

> Thanks very much Scott,
> I'm glad to get an idea of the kind of doses people are using these days. I read Jay Amsterdam's paper on high doses of Parnate.
> I'm also glad to see people using TCAs with MAOIs. I've tried practically everything as an adjunct with little success. A tri-cyclic may be in the future.

> >I have come across some research studies that indicate that Parnate begins to do things at high dosages that it does not do at lower dosages that are unrelated to MAO inhibition. One such effect is the downregulation of 5-HT2 receptors, something that occurs with several other antidepressants. Unlike Nardil, Parnate has been shown to produce a decrease in dopamine D2 receptor densities.

> Scott -could you elaborate on what this downregualtion might mean to the patient.

No. The best I can do is offer associations between the observations made in lab experiments. I think this is pretty much where things are at right now. For example, before the age of SSRIs, it was thought to be necessary that an antidepressant exert a direct effect at NE neurons and produce a downregulation of postsynaptic NE beta-1 (and not beta-2) receptors. The time course of this downregulation is observed to occur about two weeks from initial exposure to the drug. This, of course, seems to mirror the time course of the onset of clinical antidepressant activity. Well, guess what? SSRIs, without directly affecting the NE nerve synapse (at least not that has yet been observed, to my knowledge), somehow produces a downregulation of NE beta-1 receptors that takes two weeks occur. This is nothing more than an association of observations for which there is not yet an adequate understanding. It looks pretty important, though. But where does it fit into the explanation of what causes depression and how to treat it?

I know I sound like a broken record, but, "We are not there yet."

> My knowledge of neurobiology (as well as my Neurobiology itself) is not what it used to be.

What did it used to be? I am perpetually amazed at the level of knowledge and understanding that Babblers possess without having a formal education in the field. I have none.

> I don't think I could tell an Axon from a Dendrite without a microscope (that's an attempt at humor).

:-) Thanks for the tip-off. The way I am feeling this morning, I doubt I could distinguish comedy from trajedy. Actually, I think we all do a pretty good job of combining the two. For me, it is a survival strategy. By the way, what's a dendrite? (That's an attempt at humor too).

Nice talking to you.


- Scott

 

Re: High doses of Parnate-SLS?

Posted by Judy on October 22, 2000, at 14:10:26

In reply to Re: High doses of Parnate, posted by SLS on October 21, 2000, at 18:30:50

Hi Scott,
Long time no see. Last time I was here, you were very helpful to me with suggestions for augmenting Parnate when I had to quit my beloved Nardil because of the side effects. By the way, you were absolutely right about the ability to achieve orgasm returning after several months. What you didn't mention, or maybe this is only in my case, is that even if the mechanics return to working order, you don't really care.

I'm still taking Parnate alone (with Xanax at night to get about 5 hours of sleep). None of the combinations I've tried (lithium, thyroid, estrogen) made an appreciable difference, so I read with interest this thread about higher doses. I'm taking 70 mg per day right now and have just got the go-ahead to try 80 although my doctor didn't seem to think it would make any difference in my mood. So I was particularly curious about your statement:

>I have come across some research studies that indicate that Parnate begins to do things at high dosages that it does not do at lower dosages that are unrelated to MAO inhibition.

Can you be a bit more specific about that in layman's terms? Good things or bad things? I have no clue what deregulation means to me.

I just saw my doctor last week and he agreed that, for me, Parnate is "as good as it's going to get." I don't respond to anything but MAOI's and Nardil and Marplan have been ruled out because of the severe edema, myoclonus , and other nasty physical side effects they began to cause. That's pretty upsetting since I'm tolerating Parnate relatively well and I'm not really depressed but I am apathetic and anhedonic and I can't deal with accepting the way I feel right now as the best it's ever going to be.

Please translate for me your understanding of what you've read about taking higher doses of Parnate.

Thanks,
Judy

 

Re: High doses of Parnate Steeler Steeler Tookahn

Posted by Tori on October 23, 2000, at 3:34:39

In reply to Re: High doses of Parnate, posted by Steeler Tookahn on October 21, 2000, at 15:34:44

Hi there,

I was having major problems with insomnia recently (3 hours of sleep a night) and I found if I take it at 9 a.m. and 9 p.m. it has enabled me to sleep pretty much a full night's sleep. I'm on 40 mg/day.

Hope this helps. :-) Tori

 

Re: High doses of Parnate Steeler Tori

Posted by Judy on October 24, 2000, at 7:36:39

In reply to Re: High doses of Parnate Steeler Steeler Tookahn, posted by Tori on October 23, 2000, at 3:34:39

Thanks Tori, but it seems that I only sleep five hours when I'm taking MAOI's no matter what time I take them. When I was taking Nardil, I didn't mind at all. I had so much energy that I couldn't wait to get out of bed in the morning and get going. Not so with Parnate - I always seem to be dragging and I'm hoping I can find some kind of augmentation that will give me some energy.
I wish you good luck with Parnate. It can be some people's miracle drug. Judy

 

Re: High doses of Parnate Judy

Posted by Tori on October 24, 2000, at 9:14:42

In reply to Re: High doses of Parnate Steeler Tori, posted by Judy on October 24, 2000, at 7:36:39

Well, after four hours sleep this night I may be back in the same boat with you as well.

Sunday I slept the entire day. I was so exhaused. Then I went hypertensive that evening., 174/87 at 10:00 - all of a sudden I felt my chest/throat get really heavy. Constant monitoring and two doses of 30 mg adalat two hours apart and finally at 2 a.m. it was down to 89/58. Fun fun. I have no idea what caused it. I'm just glad I didn't get a headache with it (ooooh, those huuuurt!).

:-)

 

Re: High doses of Parnate-SLS?

Posted by dennison on January 31, 2001, at 12:48:29

In reply to Re: High doses of Parnate-SLS?, posted by Judy on October 22, 2000, at 14:10:26

In reply to the higher doses of tranylcypromine a.k.a. parnate . There has been some encouraging results with higher doses 90mg-130mg in refractory depressions. The main benefit to these higher doses has ironically been a lessening of any side-effects that were experienced at the lower doses that resulted from the functional sympathetic block that maoi's cause. This sympathetic block at lower doses is caused mainly from replacement of norepinephrine by octapamine which has only 1% of the functionality of norepinephrine itself. The higher doses seem to not manifest this sympathetic block--therefore the problem with low blood pressure and when standing and the lethargy which it produces is avoided.It has been postualated that the lessening of this sympathetic block phenomena is due to the higher parnate having a more pronounced sympathomimetic effect thus reversing or preventing the sympathetic block that occurs at lower doses. You need to work closely with your doctor if you are interested in these high dose parnate doses,but if you are experiencing unresponsiveness or rather severe side-effects at the lower doses 30-60 discussing the higher dose option may well be worthwhile.

 

Re: High doses of Parnate-SLS? dennison

Posted by SLS on January 31, 2001, at 20:38:55

In reply to Re: High doses of Parnate-SLS?, posted by dennison on January 31, 2001, at 12:48:29

Hi Dennison.

Would you be kind enough to answer a few questions regarding tranylcypromine and octopamine?

1. Is the route of the tranylcypromine-induced increase of octopamine formation produced via PEA metabolism, or is it the result of an inhibition of an enzyme directly responsible for its degradation?

2. Does octopamine displace NE in synaptic vesicles and act as a false transmitter?

3. Are any of the PEA-related substances products of the metabolism of tranylcypromine?

Dosages of tranylcypromine in excess of 200mg have occasionally been needed to produce a response in treatment-resistant cases.

Thanks for any reply.


- Scott


> In reply to the higher doses of tranylcypromine a.k.a. parnate . There has been some encouraging results with higher doses 90mg-130mg in refractory depressions. The main benefit to these higher doses has ironically been a lessening of any side-effects that were experienced at the lower doses that resulted from the functional sympathetic block that maoi's cause. This sympathetic block at lower doses is caused mainly from replacement of norepinephrine by octapamine which has only 1% of the functionality of norepinephrine itself. The higher doses seem to not manifest this sympathetic block--therefore the problem with low blood pressure and when standing and the lethargy which it produces is avoided.It has been postualated that the lessening of this sympathetic block phenomena is due to the higher parnate having a more pronounced sympathomimetic effect thus reversing or preventing the sympathetic block that occurs at lower doses. You need to work closely with your doctor if you are interested in these high dose parnate doses,but if you are experiencing unresponsiveness or rather severe side-effects at the lower doses 30-60 discussing the higher dose option may well be worthwhile.

 

Re: High doses of Parnate-SLS?

Posted by dennison on January 31, 2001, at 21:37:27

In reply to Re: High doses of Parnate-SLS?, posted by dennison on January 31, 2001, at 12:48:29

Hi scott--regarding your questions concerning tranylcypromine: Octopamine is the main false neuro-transmitter that is formed inside the cell as the main function of maoi "mono-amine-oxidase" which of course is blocked by parnate is to maintain metabolic purity of neurotransmitter production. When it is blocked many so called false neurotransmitters built in amounts that normally would be metabolized by mao enzmye. Octopamine is beta-hydroxylated tyramine. Tyramine oddly enough although to be strictly avoided dietarily in any significant amounts still is produced from dietary tyrosine. This tyramine is taken up into the cell and serves as a substrate for beta-hydroxylation forming octopamine in high amounts. This conc. of octopamine indeed displaces intragranular norepinephine. Then when the normal norepinephrine is to be released into the synaptic cleft"synapse" octopamine is released instead of normal norepinephrine. Since octopamine is nearly totally ineffective (1%of the potency of norepinephrine)at stimulating post-synaptic receptors functionally the peripheral autonomic nervous system effect is totally abolished. Hence the low blood pressure---reduced cardiac output from venous pooling etc. As in regards to your reference to pea as a possible metabolite of tranylcypromine itself, the normal

breakdown product is cinnamon aldehyde. Now of course parnate itself causes huge increases of (PEA) by it's direct blockade of mono-amine oxidase B which is the main enzyme metabolizing phenylethylamine(PEA). Pea is a trace amine normally just as octopamine is normally a trace amine it is well known that maoi's cause hugh increases in trace amines (another is tryptamine). P.S. --the reason that phenylethylamine type byproducts of parnate itself are not seen is because parnate has been shown not to undergo cyclopropyl ring opening which would be necessary to form the phenylethylamine backbone,instead cinnamon aldehyde is the breakdown product of parnate.


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