[pete69]

guys,
just been to shrink and we had a good old chat about my nardil-i then mentioned the half life of it and he got his maudsley hospital med book out and it listed all the anti depressants and there half lifes. was amazed to see that nardil has the shortest at 1.5hours! where something like seroxat has 3 days. so i have been advised to take my 60mg in 4 seperate doses to benefit from the short half life -so its in my system all day then..

any thoughts?

 

[IllusionalFate]

The short half life has no impact on how long the effects last. Phenelzine irreversibly binds to MAOs and permanently disables them. That means that as long as you don't skip a day or two of taking it, you should feel a pretty consistent antidepressant/prosocial effect.

The dosing schedule that I found worked the best was taking half the dose in the morning, and the other half right before you go to bed. If you take an odd number of pills per day (ie. 45mg, 75mg), take one more pill at night than you do in the morning.

 

[pete69]

thanks for the reply-my shrinks suggestion of 4 times a day was based on the short half life.
he isnt to familiar with nardil even thou hes been in practice 30+ years .
i think your 2 in morning and 2 at bedtime is a better idea.
he is learning everytime i visit him and my positive results have got him thinking of prescribing others to nardil rather than the harsh ssris and all the harsh side effects.

 

[jim_morrison]

thanks for the reply-my shrinks suggestion of 4 times a day was based on the short half life.
he isnt to familiar with nardil even thou hes been in practice 30+ years .
i think your 2 in morning and 2 at bedtime is a better idea.
he is learning everytime i visit him and my positive results have got him thinking of prescribing others to nardil rather than the harsh ssris and all the harsh side effects.

I'm suprised that your shrink isnt familiar with nardils pharmacology after 30 years of practice. I would have thought that even if he never prescribed it, he would have been required to learn about it, or atleast be interested enough to learn about it, considering his profession.

 

[RockiNToM]

rocknroll714, you massive geek you.

 

[pete69]

I'm suprised that your shrink isnt familiar with nardils pharmacology after 30 years of practice. I would have thought that even if he never prescribed it, he would have been required to learn about it, or atleast be interested enough to learn about it, considering his profession.

he said he has never started someone on nardil only carried on with there script,mostly he is in favour of the old tryc and snri meds-nardil was a last resort-obviously i tend to read up more on a drug im taking and gain knowledge on forums such as this.
he on the other hand just has the usual literature i guess,but yeah once he found the half lifes section he started reading out all the others!!!! it was like oh this is interesting i should read more on this....maybe in his day they got by on a few exams and the like.

dont get me wrong he aint 65 or summin just he aint a youngster either-them ****ers would never give nardil just out of med school

 

[Cast Away]

You would be suprised how many 30+ year psychiatrists there are out there that dont know much about nardil.

 

[robotaffliction]

well, the nardil has a metabolite that inhibits GABA transaminase reversibly, and this one has a half-life of about 12 hours. so in theory, dosing more often could help, since this metabolite has an anxiolytic effect. to dose multiple times a day would keep things more even for this effect, while for the primary effect (MAO inhibition) there is no difference

 

[robotaffliction]

Wait, it's reversible?? Not irreversible? Whoa I didn't know that. You got any sources? Not that I don't believe you, I just wanna check it out lol.

when i was at university in sweden (where i had free access to full text PDFs for lots of the journals) i read an article that described the acute and long-term effects of phenelzine on neurotransmitter levels in rats. for GABA, GABA levels (which were about 200% elevated at whatever dose they used) returned to normal "baseline" about 48 hours after the last dose. i believe its in this article http://www.ncbi.nlm.nih.gov/pubmed/1610412 but since i don't have full text access right now i can't go through the PDF and check. i might have a couple PDFs saved locally though. this one seems good too:

Neurochemical effects of the monoamine oxidase inhibitor phenelzine on
brain GABA and alanine: A comparison with vigabatrin

Kathryn G. Todd and Glen B. Baker
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Canada

btw, the group at Department of Psychiatry, University of Alberta, Edmonton, Canada that wrote these articles has a lot of focus on phenelzine and the MAOIs. the fact that pretreatment with another MAOI (parnate) can block most of the GABA elevating effect suggests that the metabolite PEH that is produced from a secondary MAO reaction is largely responsible for the GABA-T inhibition.

also, GABA-T is B6-dependent like a lot of the other enzymes nardil inhibits (B6 is a cofactor bound inside of the protein), so i'm not sure if phenelzine (or its metabolites) directly destroys B6 or destroys B6 inside of the enzyme core...

as to the MAOI properties, there is some clue to the mechanism of how phenelzine might work based on a crystal structure of MAO-B in complex with reacted phenylethylhydrazine. it appears that the hydrazine binds directly to the cofactor FAD+ (flavin-adenine dinucleotide, a sort of single-stranded two base DNA analogue), leaving behind just phenylethane:
http://www.pdb.org/pdb/explore.do?structureId=2VRL

as to how tranylcypromine acheives MAO inhibition, check out this one (it's quite similar mechanism, covalent modification of FAD+):
http://www.pdb.org/pdb/explore.do?structureId=1OJB

this is pretty much zero-day sh*t, i had checked the PDB a few weeks ago and a lot of this stuff wasn't available yet

the reason why they use MAO-B and not A in these structures (there's actually quite a lot of them if you just search for "monoamine oxidase"), is probably just that it was easier to crystallize MAO-B (MAO enzymes are usually bound to mitochondrial membranes, so to make an MAO that crystallizes in solution can be tricky experimentally). also if you search for the individual compounds (tranylcypromine, phenethylhydrazine) there are complexes of other amine oxidases bound to these substrates, as well as another FAD-containing enzyme LSD1 (lysine-specific demethylase)...