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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Questionmark on May 19, 2003, at 21:52:06
Okay, Parnate (tranylcypromine) is known to be considerably stimulating and obviously is for myself so far. However, the latest study/studies have found that it most likely does not have an amphetamine as its metabolite. So do you think its stimulating effects are a result of its MAO inhibition (particularly of MAO-B maybe?), or do you think tranylcypromine itself is a catecholamine (DA and/or NE) agonist or reuptake inhibitor, or do you think it may have a metabolite that, while not an amphetamine, is a catecholamine agonist or reuptake inhibitor?
If anyone has any ideas it would be greatly appreciated, because i am quite curious.
Posted by Paulie on May 20, 2003, at 12:18:58
In reply to Parnate pharmacology., posted by Questionmark on May 19, 2003, at 21:52:06
I noticed more stimulation on 20mg/d parnate than on 45mg/d nardil. What's interesting is that on nardil my MAO inhibition must have been anywhere in the range of approx. 40-95%. On parnate MAO inhibition was probably no greater than 25%. This data is from http://www.vh.org/adult/provider/psychiatry/CPS/17.html
There is also a chart correlating parnate dosing with MAO inhibition-http://www.vh.org/adult/provider/psychiatry/CPS/17Figure2.htmlThis is total MAO activity. Wish they had separated into MAO-A and MAO-B. Being that parnate is very dopaminergic it probably is a much stronger MAO-B inhibitor than nardil.
There was a person who overdosed on 400mg parnate. Autopsy showed no trace of any amphetamine metabolites.
Being chemically related to amphetamine may account for some stimulant effect. It could possibly be a catecholamine activity enhancer like deprenyl even at very low doses is believed to be.Paul
Posted by SLS on May 20, 2003, at 13:00:15
In reply to Re: Parnate pharmacology., posted by Paulie on May 20, 2003, at 12:18:58
> I noticed more stimulation on 20mg/d parnate than on 45mg/d nardil.
I have been on both Nardil and Parnate a few times in the past. I have also discontinued them with a rapid taper over the course of a week. Of the two, Parnate is the one for which discontinuation led to severe fatigue. I would surmise that this is an indication that Parnate or its metabolites possesses some stimulant-like properties in addition to MAO inhibition. The fatigue lasted for one to two weeks.
- Scott
Posted by cybercafe on May 20, 2003, at 18:00:49
In reply to Re: Parnate pharmacology., posted by Paulie on May 20, 2003, at 12:18:58
> I noticed more stimulation on 20mg/d parnate than on 45mg/d nardil. What's interesting is that on nardil my MAO inhibition must have been anywhere in the range of approx. 40-95%. On parnate MAO inhibition was probably no greater than 25%. This data is from http://www.vh.org/adult/provider/psychiatry/CPS/17.html
> There is also a chart correlating parnate dosing with MAO inhibition-http://www.vh.org/adult/provider/psychiatry/CPS/17Figure2.html
>
> This is total MAO activity. Wish they had separated into MAO-A and MAO-B. Being that parnate is very dopaminergic it probably is a much stronger MAO-B inhibitor than nardil.
> There was a person who overdosed on 400mg parnate. Autopsy showed no trace of any amphetamine metabolites.
> Being chemically related to amphetamine may account for some stimulant effect. It could possibly be a catecholamine activity enhancer like deprenyl even at very low doses is believed to be.
>
> Paul
>
maybe nardil is less stimulating because it leads to an increase in GABA?
Posted by djmmm on May 20, 2003, at 18:14:24
In reply to Re: Parnate pharmacology., posted by Paulie on May 20, 2003, at 12:18:58
> I noticed more stimulation on 20mg/d parnate than on 45mg/d nardil. What's interesting is that on nardil my MAO inhibition must have been anywhere in the range of approx. 40-95%. On parnate MAO inhibition was probably no greater than 25%. This data is from http://www.vh.org/adult/provider/psychiatry/CPS/17.html
> There is also a chart correlating parnate dosing with MAO inhibition-http://www.vh.org/adult/provider/psychiatry/CPS/17Figure2.html
>
> This is total MAO activity. Wish they had separated into MAO-A and MAO-B. Being that parnate is very dopaminergic it probably is a much stronger MAO-B inhibitor than nardil.
> There was a person who overdosed on 400mg parnate. Autopsy showed no trace of any amphetamine metabolites.
> Being chemically related to amphetamine may account for some stimulant effect. It could possibly be a catecholamine activity enhancer like deprenyl even at very low doses is believed to be.
>
> Paul
>I think Parnate has some agonist properties, in adition to it's primary MAO inhibition, it has some use as an antiparkinsonian med. Unfortunately that chart is a little misleading since the dose is mg/kg in relation to weight. At a theraputic dose, either MAOI will irreversibly bond to monoamine oxidase A and B in the 80% range. Even still, the majority of studies on MAO inhibition show little correlation between the theraputic effects of MAOIs and the % of inhibition.
Parnate and Nardil are very different drugs, with numerous metabolites, phenylethylidenehydrazine, a metabolite of Nardil, increases GABA levels, this is unique to phenelzine, as is its ability to downregulate 5-ht2 receptors. Phenelzine is also unique in that it seems to greatly increase serotonin levels (after long term treatment) while levels of catecholamines remain lower (although obviously increased)..and this variation is independent of nearly equal MAO-A/MAO-B inhibition.
After being on both meds Parnate is more stimulating, in a classical stimulant way (at times my eyes were dialated, my heart beat a little faster, etc) While Nardil, although far from sedating, had a mild euphoric quality, I suppose due to it's effects on GABA.
Posted by Jack Smith on May 20, 2003, at 18:57:57
In reply to Re: Parnate pharmacology., posted by djmmm on May 20, 2003, at 18:14:24
> While Nardil, although far from sedating, had a mild euphoric quality, I suppose due to it's effects on GABA.
Djmmm,
That is an interesting comment. How do you think its GABA effect could produce a mild euphoric quality? I have, at times, found a mild euphoric quality to xanax but not to any other benzos, all of which, I understand affect GABA.
JACK
Posted by Questionmark on May 21, 2003, at 0:42:28
In reply to Re: Parnate pharmacology., posted by Paulie on May 20, 2003, at 12:18:58
Thank you all for your responses. Cybercafe said something interesting: "maybe nardil is less stimulating because it leads to an increase in GABA?" i never thought of that. What if it would be just as stimulating as Parnate except for its effects on GABA? No, probably not. Cuz Marplan would be stimulating too. And yeah as someone said Parnate feels much like a typical stimulant.
Three of you said that you thought Parnate probably has catecholamine- agonist properties. Now that i think about it, i think that's probably right. But that makes me angry. i'm sick of stimulants. i'm sick of the false hope and confidence they give me. Not to mention the anxiety and appetite suppression. i'm sick of stimulants. i just want an antidepressant, not a euphoriant. Wow, have i changed. Okay enough rambling.
Posted by Caleb462 on May 23, 2003, at 6:13:55
In reply to Re: Parnate pharmacology., posted by Questionmark on May 21, 2003, at 0:42:28
> Thank you all for your responses. Cybercafe said something interesting: "maybe nardil is less stimulating because it leads to an increase in GABA?" i never thought of that. What if it would be just as stimulating as Parnate except for its effects on GABA? No, probably not. Cuz Marplan would be stimulating too. And yeah as someone said Parnate feels much like a typical stimulant.
> Three of you said that you thought Parnate probably has catecholamine- agonist properties. Now that i think about it, i think that's probably right. But that makes me angry. i'm sick of stimulants. i'm sick of the false hope and confidence they give me. Not to mention the anxiety and appetite suppression. i'm sick of stimulants. i just want an antidepressant, not a euphoriant. Wow, have i changed. Okay enough rambling.Well, cathecolamine-agonist really isn't the correct term, but I believe Parnate probably does have some psychostimulant properties. It doesn't metabolize into amphetamine or methamphetamine, but it IS a related drug, and thus it can be assumed that it has similiar actions. Not neccesarilly of course, but very possible.
Posted by djmmm on May 23, 2003, at 9:43:01
In reply to Re: Parnate pharmacology., posted by Caleb462 on May 23, 2003, at 6:13:55
> > Thank you all for your responses. Cybercafe said something interesting: "maybe nardil is less stimulating because it leads to an increase in GABA?" i never thought of that. What if it would be just as stimulating as Parnate except for its effects on GABA? No, probably not. Cuz Marplan would be stimulating too. And yeah as someone said Parnate feels much like a typical stimulant.
> > Three of you said that you thought Parnate probably has catecholamine- agonist properties. Now that i think about it, i think that's probably right. But that makes me angry. i'm sick of stimulants. i'm sick of the false hope and confidence they give me. Not to mention the anxiety and appetite suppression. i'm sick of stimulants. i just want an antidepressant, not a euphoriant. Wow, have i changed. Okay enough rambling.
>
> Well, cathecolamine-agonist really isn't the correct term, but I believe Parnate probably does have some psychostimulant properties. It doesn't metabolize into amphetamine or methamphetamine, but it IS a related drug, and thus it can be assumed that it has similiar actions. Not neccesarilly of course, but very possible.There is still a multitude of information to learn about MAO inhibitors, they are complex drugs because MAO is a complex enzyme, and there are most definitely other amines (trace or otherwise) effected. There is evidence that tranylcypromine binds to reuptake pumps (5-ht, DA and NE). I came across an old study on pubmed which stated that tranylcypromine and phenelzine released norepinephrine from stores, while the MAOIs pargyline and iproniazid did not, and studies of tranylcypromine that stated dopamine release was part of it's pharamacology.
When studying something as broad a monoamine oxidase, it is nearly impossible (at this time) to completely determine the function (and resulting effects) of inhibiting this enzyme (afterall, it's found in the brain, heart and liver)
Posted by Questionmark on May 23, 2003, at 23:16:04
In reply to Re: Parnate pharmacology., posted by djmmm on May 23, 2003, at 9:43:01
>"There is still a multitude of information to learn about MAO inhibitors, they are complex drugs because MAO is a complex enzyme, and there are most definitely other amines (trace or otherwise) effected. There is evidence that tranylcypromine binds to reuptake pumps (5-ht, DA and NE). I came across an old study on pubmed which stated that tranylcypromine and phenelzine released norepinephrine from stores, while the MAOIs pargyline and iproniazid did not, and studies of tranylcypromine that stated dopamine release was part of it's pharamacology."
Wow, that's the kind of information i was looking for, thank you. It seems true too. That's kind of disappointing though. i wonder what just a pure irreversable MAO inhibitor would be like. i also wonder if phenelzine has any serotonin reuptake inhibiting properties as well.
This is the end of the thread.
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