Psycho-Babble Medication Thread 1062156

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How can the half-life of Marplan be unknown? SLS?

Posted by PeterMartin on March 10, 2014, at 0:16:52

I've searched all over and am unable to find the half life for Marplan. Whether it matters or not (Re: a previous thread here about this said halflife shouldn't matter w irreversible maois) isn't hakf-life standard drug information? The drug has has been around since the 60s.....

Sorry to tag you specifically SLS but I love your insight on this forum. I also remember you did a trial of it a little while back. Any guesses?

Thanks!!

 

Re: How can the half-life of Marplan be unknown? SLS? PeterMartin

Posted by SLS on March 10, 2014, at 0:38:51

In reply to How can the half-life of Marplan be unknown? SLS?, posted by PeterMartin on March 10, 2014, at 0:16:52

> I've searched all over and am unable to find the half life for Marplan. Whether it matters or not (Re: a previous thread here about this said halflife shouldn't matter w irreversible maois) isn't hakf-life standard drug information? The drug has has been around since the 60s.....
>
> Sorry to tag you specifically SLS but I love your insight on this forum. I also remember you did a trial of it a little while back. Any guesses?

I could not find the half-life of Marplan when I added it to my drug chart. As you know, Marplan and Nardil are both hydrazine compounds. Parnate is not. Parnate has a half-life of 1 - 3 hours. Nardil has a half-life of at least 12 hours after a single dose. However, Nardil inhibits its own metabolism because it inhibits MAO. At equilibrium, my guess is that the half-life of Nardil is significantly longer. Does this also occur with Marplan, taking into consideration that, like Nardil, it is a hydrazine? I don't know.

I would take Marplan at least twice a day to help avoid side effects. I found Marplan to be a remarkably "clean" drug. I hardly knew that I was taking it. Unfortunately, my response to it was inadequate, and I ultimately discontinued it.

I hope this was helpful. What was your reason for wanting to know the 1/2 life of Marplan?


- Scott

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by PeterMartin on March 10, 2014, at 1:09:08

In reply to Re: How can the half-life of Marplan be unknown? SLS? PeterMartin, posted by SLS on March 10, 2014, at 0:38:51

Fantastic reply - thanks.

The suggestion to take it twice a day is probably what I was after. My doc is the type that says if it makes you tired take it at night, if it keeps you up take it in the morning.....kinda leaves it up to me. I've been taking it since 2010 but I responded well to 20mg when it was added to my lamictal/seroquel regime. At some point I went up to 30mg. I've always taken it as one dose at night.

Ive had some breakthrough depression the last few months so I've been trying 40 and now 50mg over the past month. Since it only comes in 10mg I decided to try the extra 10/20mg in the morning and continue to take 30 at night. Doing that though the last few days I've had flashes of feeling good followed by really spacey/down periods. I'd like to give the dose a fair trial over a period of weeks as my body is probably just adjusting. Im justbhoping to have at least a little logic behind either dividing or taking it all at night. I'll probably stick with this (30 at night / 20 in the am) for another few weeks and see how it goes.

Still bizarre to me that there isn't more data about how long it takes to break down.

Appreciate the quick reply. Have read many of your posts since 2005 and love your insight.


 

Re: How can the half-life of Marplan be unknown? SLS? PeterMartin

Posted by SLS on March 10, 2014, at 7:59:27

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by PeterMartin on March 10, 2014, at 1:09:08

> Fantastic reply - thanks.
>
> The suggestion to take it twice a day is probably what I was after. My doc is the type that says if it makes you tired take it at night, if it keeps you up take it in the morning.....kinda leaves it up to me. I've been taking it since 2010 but I responded well to 20mg when it was added to my lamictal/seroquel regime. At some point I went up to 30mg. I've always taken it as one dose at night.
>
> Ive had some breakthrough depression the last few months so I've been trying 40 and now 50mg over the past month. Since it only comes in 10mg I decided to try the extra 10/20mg in the morning and continue to take 30 at night. Doing that though the last few days I've had flashes of feeling good followed by really spacey/down periods. I'd like to give the dose a fair trial over a period of weeks as my body is probably just adjusting. Im justbhoping to have at least a little logic behind either dividing or taking it all at night. I'll probably stick with this (30 at night / 20 in the am) for another few weeks and see how it goes.
>
> Still bizarre to me that there isn't more data about how long it takes to break down.
>
> Appreciate the quick reply. Have read many of your posts since 2005 and love your insight.


If taking Marplan all at once in the evening works for you, and your burden of side effects remains minimal, I don't know of any reason why you cannot do this. I have heard of people taking Parnate once a day. I am a bit of a stickler for maintaining a constant blood level, but this may not always be that important. Parnate must produce a peak concentration in the brain very quickly. It enters, binds irreversibly, and disappears out of the blood stream, leaving behind the inactivated enzymes permanently disabled. (There is some debate about the absolute irreversibility of Parnate). Personally, I like to see a drug have a half-life of 18 or more hours before dosing once a day. This is arbitrary on my part, though. Lamictal has a half-life of 25 hours (when given without enzyme inducers or inhibitors), but I don't feel right unless I take it twice a day.

I hate to see you push yourself through several weeks of feeling spacy with twice-a-day dosing if once-a-day dosing would be better. I will say this, though. Feeling spacy is often a prelude to my responding to Nardil. This could be happening to you, now that you have increased the dosage. For me, feeling weird can be a good thing. Also, insomnia has always been a good sign. I wish I had responded well to Marplan. It really was clean compared to Nardil and Parnate.

Good luck.


- Scott

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by rose45 on March 21, 2014, at 16:31:51

In reply to Re: How can the half-life of Marplan be unknown? SLS? PeterMartin, posted by SLS on March 10, 2014, at 7:59:27

Scott, What do you mean by ' clean.'
Are any drugs 'clean' ?

 

Re: How can the half-life of Marplan be unknown? SLS? rose45

Posted by SLS on March 21, 2014, at 19:49:35

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by rose45 on March 21, 2014, at 16:31:51

> Scott, What do you mean by ' clean.'
> Are any drugs 'clean' ?

Are any drugs "clean"?

I guess "clean" is a relative term. While I was taking Marplan, I don't recall having any side effects at all.

Quite often, a drug that someone is taking for the first time will produce startup side effects that often dissipate over time. Nortriptyline was that way with me. When I first started it, it produced profound sleepiness along with dry mouth, and increased heart rate. Over time, these things have resolved for the most part. On a daily basis, I never notice that I am taking the drug. I much prefer the side effects of desipramine and nortriptyline than those of the SSRIs.


- Scott

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by tom2228 on March 21, 2014, at 21:15:39

In reply to Re: How can the half-life of Marplan be unknown? SLS? PeterMartin, posted by SLS on March 10, 2014, at 7:59:27

I take Marplan (50mg) and I took have been baffled how a product approved by the FDA (reapproved in 2007) has such scant information that pertains to safety. E.g., if Marplan or its metabolites inhibits or induces any of the CYP450 isoenzymes, that could have clinical implications for those of us on other meds.

Marplan has been the best fit out of the MAOIs for me. It seems to lack the other "extra" properties that Nardil and Parnate have.. I wonder whether Marplan has other other properties other than MAO inhibition that aren't yet known of -- I would like to study this in my future if the funds for such a "dead horse" can be appropriated.

From what I have seen in digging through pub med is that the MAO inhibition seems to come from one of the metabolites rather than isocarboxazid itself. How long these compounds last, in the body i.e. whether they have more acute or more chronic affects aside from MAO inhibition is a mystery at this point, at least to me; many of the articles are old and don't even have abstracts available let alone free full texts.

I have found two things about the "extra" properties of Marplan. It seems that

1) one of the main metabolites, benzylhydrazine inhibits dopamine beta-hydroxylase, which metabolizes dopamine to norepinephrine and thereby epinephrine.

http://www.ncbi.nlm.nih.gov/pubmed/3007460
http://www.ncbi.nlm.nih.gov/pubmed/1868089

There are also articles on pubmed about DBH and depression/ anxiety.


2) benzylhydrazine, also activates tryptophan pyrrolase (tryptophan oxygenase), which metabolizes tryptophan and thereby indirectly modulates serotonin production.

http://www.ncbi.nlm.nih.gov/pubmed/1244108

Perhaps there is some variance this respect:
http://www.ncbi.nlm.nih.gov/pubmed/4736089

According to wiki ( http://en.wikipedia.org/wiki/Tryptophan_2,3-dioxygenase#Disease_relevance )
"Another study showed that tryptophan 2,3-dioxygenase is potentially involved in the metabolic pathway responsible for anxiety-related behavior.[16] Generating mice deficient for tryptophan 2,3-dioxygenase and comparing them to the wild type, the group found that the tryptophan 2,3-dioxygenase-deficient mice showed increased plasma levels not only of tryptophan, but also of serotonin and 5-HIAA in the hippocampus and midbrain. A variety of tests, such as elevated plus maze and open-field tests showed anxiolytic modulation in these knock-out mice, the findings demonstrating a direct link between tryptophan 2,3-dioxygenase and tryptophan metabolism and anxiety-related behavior under physiological conditions."


The clinical significance of these effects I do not know. It would make a difference whether they were from isocarboxazid or one of the metabolites and would help to know the half-lives to determine whether these effects are more acute in nature, giving the drug "waves" or more chronic effects. This could influence whether it would be best to take it all at once, a few times, or spread very evenly throughout the day, depending on what effects are desirable.

What I have found about the main metabolite benzylhydrazine:

https://www.jstage.jst.go.jp/article/jphs1951/22/5/22_5_629/_pdf

"Tissue levels of benzylhydrazine show a maximum at 30 min and then gradually decline to undetectable levels within 24 hr after dosing. Remarkable inhibition of tissue MAO activities was recognized despite disappearance of the drug from the tissues at 24 hr."

"As shown in Table 2, tissue benzylhydrazine levels elevated significantly within 1-2 hr after
treatment, then decreased gradually to lower or undetectable levels at 24 hr."

"This inhibitory effect of benzylhydrazine formed from isocarboxazid on tissue MAO activity was initiated within 15 min after drug administration."

Hope this helps

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by PeterMartin on March 31, 2014, at 13:51:45

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by tom2228 on March 21, 2014, at 21:15:39

Wow that was great! Thanks!

How did you settle at 50mg? Did you try 40mg for a while and step up or were you quick to reach that dose and just stick with it?

Can I also ask when you take it? Divided doses?

Thanks!!

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by tom2228 on March 31, 2014, at 15:01:52

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by PeterMartin on March 31, 2014, at 13:51:45

> Wow that was great! Thanks!
>
> How did you settle at 50mg? Did you try 40mg for a while and step up or were you quick to reach that dose and just stick with it?
>
> Can I also ask when you take it? Divided doses?
>
> Thanks!!

No problem, I have sort of a vested interest in Marplan. I am no longer taking it, but it's done a lot for me over the years. I just washed out and am starting notriptyline tonight because my new pdoc didn't have the guts to combine the two and depression had gotten much worse.

I actually started at 20mg and stayed for about 3/4 year, then I got up to 30mg at a rehab when I recognized my leftover dysthymia was related to my use of drugs. A year later in a major depressive episode I went up to 40mg. I did well for another year and was taken off Marplan when incarcerated. I then trialed Nardil and retrialed Parnate. I was unhappy with the results and wished to return to Marplan.

Having put a lot of effort and time into my recovery from substance use at this point and with a clearer perspective on the severity of my mental health, my expectations for antidepressive treatment had changed. I realized I had been accepting sub-par symptom coverage because it had been the best coverage I had had before and simply didn't know any better. I recognized the importance of trying to achieve full remission and decided to aim for 50mg.

I always took it twice a day. The latest was 30mg in the morning and 20mg at 2pm.

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by PeterMartin on October 3, 2015, at 12:44:56

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by tom2228 on March 31, 2014, at 15:01:52

Finally found the answer to my own question:

Pharmacokinetics
Oral absorption of Isocarboxazid is found to be 60.5% 9.5. Presystemic metabolism is noted to be 60.5% 9.5 and metabolism is reported Liver. Renal Excretion accounts for Urine and plasma half life is 36 hr.

via:

http://druginfosys.com/Drug.aspx?drugCode=392&drugName=

 

Re: How can the half-life of Marplan be unknown? SLS? PeterMartin

Posted by SLS on October 3, 2015, at 13:52:08

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by PeterMartin on October 3, 2015, at 12:44:56

Thanks!


- Scott

 

Re: How can the half-life of Marplan be unknown? SLS?

Posted by Escapee on October 7, 2015, at 9:56:30

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by PeterMartin on March 31, 2014, at 13:51:45

I take my entire dose of isocarboxazid in the morning. Remember that the half life is measured in the blood. Brain levels may stay higher for a lot longer.

 

Re: starting Marplan, unsure re: parnate washout tom2228

Posted by porkpiehat on October 5, 2017, at 20:14:20

In reply to Re: How can the half-life of Marplan be unknown? SLS?, posted by tom2228 on March 21, 2014, at 21:15:39

Jumping on an old thread here but my new prescriber and I have no idea what kind of washout we should do in switching me from Parnate to Marplan (if we can get my insurance to cover).

six months into parnate I am finding the amphetamine qualities combined with some other effects are ramping up compulsive behavior, as well as a good amount of detachment.

I've been mostly at 20 for the latter months with a couple of jumps to 30 when things darkened. Hopefully that will minimize washout.

I've heard a day or two would be fine but there's so little info on Marplan. I also need to know if I'm going to go through parnate withdrawl followed by the weak, zoney, MAOI ramp up nightmare so that I can plan to not plan anything important.

Big hopes for this! No generic here in the US


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