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/1868089There 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/4736089According 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
poster:tom2228
thread:1062156
URL: http://www.dr-bob.org/babble/20140307/msgs/1063013.html