![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 3 to 27 of 36. Go back in thread:
Posted by britney27 on March 23, 2008, at 19:04:50
In reply to Re: Parnate LD 50 [xxx]? » britney27, posted by Jamal Spelling on March 23, 2008, at 13:59:43
Thanks Jamal, I figured that, I am guessing now that the XXX is for people who weigh about XXX then. I might actually push for XXX, it seems like a reasonable dosage.
Posted by Deputy Racer on March 23, 2008, at 22:44:23
In reply to Parnate LD 50 [xxx]?, posted by britney27 on March 23, 2008, at 8:12:43
Please don't post any information here related to lethal doses of medications. Your post was not about how much to take to commit suicide, but the principle is the same. Please do not post lethal dosage information on this site.
If you have any questions regarding the posting policies on this site, please read the FAQ, located at http://www.dr-bob.org/babble/faq.html Follow ups to this action should be directed to the Administration board and should themselves be civil.
Dr Bob has ultimate authority over all administrative issues on this site, and may choose at any time to revise or reverse any action taken by a deputy.
Deputy Racer
Posted by Larry Hoover on March 23, 2008, at 22:45:44
In reply to Parnate LD 50 [xxx]?, posted by britney27 on March 23, 2008, at 8:12:43
> Hi,
>
> I am currently on Parnate and I am finding that it works really well but I have a tolerance towards it and I feel that I have to increase the dosage for it to remain effective. I have taken 100mg per day but read that it is possible to take up to 200mg a day but I am not sure if this is a safe dosage and whether it will cause hypertensive crisis or serotonin toxicity because I have read that the XXX.Uhhh, the Glaxo MSDS lists the oral LD50 in rats at "XXX". That's a substantial discrepancy from the figure you've presented.
In any case, what you need to do is familiarize yourself with the overdose symptoms for Parnate. The monograph lists those as: anxiety, agitation, manic symptoms, restlessness, mental confusion, insomnia and digestive disturbances. Beyond that, both hypertensive and hypotensive crisis (i.e. shock) can occur.
Lar
Posted by britney27 on March 23, 2008, at 23:12:45
In reply to Please follow board guidelines » britney27, posted by Deputy Racer on March 23, 2008, at 22:44:23
Dear Deputy Racer,
I am sorry you think I have offended the board guidelines. This is not what i intended to do and I don't think its the same principle. My issue is with regards to dosage and the link to safety, I was not implying how much do I need to take to commit suicide.
If anything, I find the other threads on Parnate concerning because they have people posting you can take 200mg + amount without any consideration for what the safety dosage is. There is even one thread stating that someone took 400mg and this is concerning as if I was naive I might actually think it would be ok to take that much.
My post seeks to clarify this concern by trying to gauge whether someone should take meds according to their body weight or whether any dose is safe (eg if x takes that much, is it ok for y to).
I would thus like Dr Bob to review my post.
Thank you
Britney.
Posted by britney27 on March 23, 2008, at 23:39:17
In reply to Re: Parnate LD 50 [xxx]? » britney27, posted by Larry Hoover on March 23, 2008, at 22:45:44
Dear Larry, where did you get the gsk less XXXmg from? I tried to obtain that info on the internet but can't find it?
What does that exactly mean anyway, does it mean anything less than XXXmg a day is safe?
cheers
Britney
Posted by Larry Hoover on March 24, 2008, at 8:19:01
In reply to Re: Parnate LD 50 [xxx]?, posted by britney27 on March 23, 2008, at 23:39:17
> Dear Larry, where did you get the gsk less XXXmg from? I tried to obtain that info on the internet but can't find it?
If you Google tranylcypromine and MSDS, it'll be on the first page.
> What does that exactly mean anyway, does it mean anything less than XXXmg a day is safe?
>
> cheers
>
> BritneyThere are a number of interpretive issues to consider. First, the toxic amount is stated in ambiguous terms. Less than XXX? How much less? I don't recall seeing a vague statement like that one on an MSDS, ever before. Also, this figure is for another species, not even in the same Order as we are, i.e. not from a primate. Generalizing toxicity from this vague information is risky.
But that's why I focussed on the symptoms of toxicity. Frankly, it doesn't matter one iota what the statistical dose for toxicity happens to be, when one individual is making that personal assessment of toxicity. 10,000 other people might get away with taking a particular dose, but if it creates symptoms of toxicity in *you*, then that's all that matters. For you, that's all that matters.
Lar
Posted by britney27 on March 24, 2008, at 8:44:41
In reply to Re: Parnate LD 50 [xxx]? » britney27, posted by Larry Hoover on March 24, 2008, at 8:19:01
> > Dear Larry, where did you get the gsk less XXXmg from? I tried to obtain that info on the internet but can't find it?
>
> If you Google tranylcypromine and MSDS, it'll be on the first page.
>
> > What does that exactly mean anyway, does it mean anything less than XXXmg a day is safe?
> >
> > cheers
> >
> > Britney
>
> There are a number of interpretive issues to consider. First, the toxic amount is stated in ambiguous terms. Less than XXX? How much less? I don't recall seeing a vague statement like that one on an MSDS, ever before. Also, this figure is for another species, not even in the same Order as we are, i.e. not from a primate. Generalizing toxicity from this vague information is risky.
>
> But that's why I focussed on the symptoms of toxicity. Frankly, it doesn't matter one iota what the statistical dose for toxicity happens to be, when one individual is making that personal assessment of toxicity. 10,000 other people might get away with taking a particular dose, but if it creates symptoms of toxicity in *you*, then that's all that matters. For you, that's all that matters.
>
> LarHi Larry, your original suggetion of less than xxxmg/kg does not refer to Tranylcypromine (parnate). My original figure was correct. Double that for full toxicity (ref Goldfranks Toxicologic emergencies). I think you were mistaken with moclobemide, another MAOI but reversible which is much much higher saftey threshold, the same amount that you suggested. I know rats are different primates but they do behave similarily to humans.
I agree with you though that knowing the symptoms of toxicity is important but even then it gets confusing because I have had some of those symptoms before and told the chemist and she said it was normal side-effects, so knowing hte safest maximum dose is still an important indicator for responsible consumption. Thanks so much for your reply though, I really do appreciate the fact that you replied to my question.
cheers
Britney
Posted by Larry Hoover on March 24, 2008, at 10:35:47
In reply to Re: Parnate LD 50 [xxx]?, posted by britney27 on March 24, 2008, at 8:44:41
> Hi Larry, your original suggetion of less than xxxmg/kg does not refer to Tranylcypromine (parnate).
Oh, it does refer to Parnate. I just searched again, and I found two different Glaxo MSDS documents for this drug. The one dated in 2001 is the one I referred to. I just found one dated 2005, which simply states that "adverse effects might occur following ingestion". I had no idea there were two different documents floating around. I stopped looking after I found the first one.
> My original figure was correct. Double that for full toxicity (ref Goldfranks Toxicologic emergencies).
Okay. I don't have access to that volume.
> I think you were mistaken with moclobemide, another MAOI but reversible which is much much higher saftey threshold, the same amount that you suggested.
Again, no. But, whatever.
> I know rats are different primates but they do behave similarily to humans.
I'm a toxicologist, Britney. You can't assume that. Standard wisdom is to implement a 1,000-fold safety factor for converting rodent tox thresholds to human exposure recommendations. And that's the exact discrepancy factor we've been discussing. I cannot assure you, however, that this is the reason the two sources differ by a factor of 1000. That would be very negligent of me.
> I agree with you though that knowing the symptoms of toxicity is important but even then it gets confusing because I have had some of those symptoms before and told the chemist and she said it was normal side-effects, so knowing hte safest maximum dose is still an important indicator for responsible consumption.
Yes, those are the typical side effects that one might experience with a dose increase. The thing is, the body has to get past them before it can adjust/accomodate to them. Toxicity in this instance is an acute experience. Statistical evidence will not accurately predict individual experience.
> Thanks so much for your reply though, I really do appreciate the fact that you replied to my question.
>
> cheers
>
> BritneyYou're welcome.
Lar
Posted by gardenergirl on March 24, 2008, at 13:34:48
In reply to Re: Parnate LD 50 [xxx]?, posted by britney27 on March 24, 2008, at 8:44:41
> so knowing hte safest maximum dose is still an important indicator for responsible consumption.Larry brings up a number of issues regarding determining safe dosing for prescription medications. These factors, along with the seriousness of the consequences of mistakes with MAOI's are exactly why it's important to work with your physician to determine appropriate dosing of prescription medications. What does your doctor recommend for you?
gg
Posted by Dr. Bob on March 24, 2008, at 20:07:15
In reply to Re: Please follow board guidelines, posted by britney27 on March 23, 2008, at 23:12:45
> I am sorry you think I have offended the board guidelines. This is not what i intended to do and I don't think its the same principle. My issue is with regards to dosage and the link to safety, I was not implying how much do I need to take to commit suicide.
The thing about an LD50 is that it can be used by some people to harm themselves as well as by others to keep themselves safe. I'm sorry you got caught by this rule when you were trying to keep yourself safe.
> My post seeks to clarify this concern by trying to gauge whether someone should take meds according to their body weight or whether any dose is safe (eg if x takes that much, is it ok for y to).
That's a good question, and fine to ask in a way that doesn't refer to the LD50. Thanks,
Bob
Posted by britney27 on March 24, 2008, at 20:16:11
In reply to Re: Parnate LD 50 [xxx]? » britney27, posted by Larry Hoover on March 24, 2008, at 10:35:47
Dear Doctor Larry,
Once again thank you so much for your response.
FYI here are the links which give you the saftey doses for Tranylcyromine and Moclobemide:
p 885 under epidemiology and also
http://www.accessmedicine.com/content.aspx?aID=601353
There are other journal articles that support these figures.
I know its not your fault but gsk were wrong with their quotation.
I have gone to 100mg per day and the side effects were bad when I first started (extreme leg restlessness), insomnia and chest pain and constriction but I sort of got used to the side effects and I feel as though I have developed a tolerance to them and need to keep going higher to get my "fix". It makes my whole body relax and calm. It almost works like an amphetamine in a sense. I did call the poisions info centre and they told me you can go to 200mg per day and the side effects I was experiencing with my chest pain was ok. Its only when you have a severe headache sudden headache that you should go to hospital. When I experience severe hypotension I just lie down on my bed for a while.
Posted by britney27 on March 24, 2008, at 20:18:33
In reply to Re: board guidelines » britney27, posted by Dr. Bob on March 24, 2008, at 20:07:15
Thanks Dr Bob, I will not refer to that.
Posted by rgb on March 26, 2008, at 10:42:30
In reply to Re: Parnate LD 50 [xxx]?, posted by britney27 on March 24, 2008, at 20:16:11
> It almost works like an amphetamine in a sense.
I vaguely remember something about metabolites with stimulant effects; if that is true (I have no idea, but it seems plausible enough given its structure), maybe these metabolites become more relevant at higher doses? But really, I have no idea.
Posted by Quintal on March 26, 2008, at 15:04:36
In reply to Parnate metabolites, posted by rgb on March 26, 2008, at 10:42:30
I think they were supposed to be mostly methamphetamine and PEA. People have been talking about this for years, but no real answers as yet. I once read a PubMed report of an autopsy where methamphetamine had been found in the body of a Parnate overdose, so it must be some truth in it. I noticed a similar effect re: dose escalation. At one point I was taking 120mg/day and it felt like getting a 'fix' from a stimulant like coke or meth. I've had a theory for a while that MAO inhibition 'augments' or amplifies the stimulant effect of the small amounts of amphetamine metabolites, so despite being produced in relatively small amounts, the metabloites actually have a substantial effect in practice. Of course I don't know if this is actually true.
Q
Posted by britney27 on March 26, 2008, at 19:09:32
In reply to Re: Parnate metabolites, posted by Quintal on March 26, 2008, at 15:04:36
> I think they were supposed to be mostly methamphetamine and PEA. People have been talking about this for years, but no real answers as yet. I once read a PubMed report of an autopsy where methamphetamine had been found in the body of a Parnate overdose, so it must be some truth in it. I noticed a similar effect re: dose escalation. At one point I was taking 120mg/day and it felt like getting a 'fix' from a stimulant like coke or meth. I've had a theory for a while that MAO inhibition 'augments' or amplifies the stimulant effect of the small amounts of amphetamine metabolites, so despite being produced in relatively small amounts, the metabloites actually have a substantial effect in practice. Of course I don't know if this is actually true.
>
> QHi Q, that is very interesting. Although I have never tried coke in my life somehow I get the feeling of what its like. Its almost like your whole body relaxes and you feel a sense of calmness...then comes the restlessness and I feel I have to move my legs up and down up and down.
So you are on 120mg a day. That is quite a large dosage. Have you been able to sustain that for a long time? I found at 100mg a day I was actually getting nauseous but the most worrying thing is that I was getting pain and tightness in my heart or heart pulpitations so I had to go back to 60mg and now I am building myself up again, lol. Do you ever get pain or tightness/restriction in the chest or heart pulpitations and is this something to worry about or is it just anxiety?
Also the first time I took it, I actually survived on 2-3 hours sleep and felt fully energised. Then I took a break from it because I actually couldn't afford it and started on it three weeks later but it actually has a sedating effect now instead of an energising effect which I think is quite weired.
cheers
Britney
Posted by Quintal on March 28, 2008, at 14:48:36
In reply to Re: Parnate metabolites, posted by britney27 on March 26, 2008, at 19:09:32
I had the tightness in my chest and palpitations too so I checked my blood pressure with a cuff I had, and it was still within the normal range. I figured it was safe. It would come on within half an hour of me taking a dose. I also had dilated pupils. I think I was taking it in divided doses of about 30-40mg at a time. A Parnate veteran once told me that single doses greater than 40mg can cause spontaneous hypertensive crises, so I'd be wary of taking too much in one go. In practice I found that the stimulant effect would wear off after a about two or three hours, and I'd usually top myself up when I felt the effect beginning to wear off.
I was only on Parnate for a few months when my pdoc pulled the plug and discharged me. Parnate does have 'abuse potential'... i.e. it gets you high given a high enough dose.
I remember waking up in the early hours of the morning after maybe three hours of sleep and getting up to walk the dogs and do some work before going to work. Like you, I felt quite energized considering I'd had so little sleep, and I had a very (physically) demanding job at that time too.
Q
Posted by Britney27 on March 28, 2008, at 21:36:55
In reply to Re: Parnate metabolites, posted by Quintal on March 28, 2008, at 14:48:36
> I had the tightness in my chest and palpitations too so I checked my blood pressure with a cuff I had, and it was still within the normal range. I figured it was safe. It would come on within half an hour of me taking a dose. I also had dilated pupils. I think I was taking it in divided doses of about 30-40mg at a time. A Parnate veteran once told me that single doses greater than 40mg can cause spontaneous hypertensive crises, so I'd be wary of taking too much in one go. In practice I found that the stimulant effect would wear off after a about two or three hours, and I'd usually top myself up when I felt the effect beginning to wear off.
>
> I was only on Parnate for a few months when my pdoc pulled the plug and discharged me. Parnate does have 'abuse potential'... i.e. it gets you high given a high enough dose.
>
> I remember waking up in the early hours of the morning after maybe three hours of sleep and getting up to walk the dogs and do some work before going to work. Like you, I felt quite energized considering I'd had so little sleep, and I had a very (physically) demanding job at that time too.
>
> QWow that describes exactly what happens to me. I have been to the Dr twice when I have had palpitations and chest pain too but my blood pressure turned out to be in the healthy range so I dismissed the symptoms as psychological such as panic attacks which I have never had prior to starting parnate or a symptom that was going to result in me having cardiovascular collapse or cardiac arrest (I am not sure what the difference is between the two). If I do have a spontaneous heart attack or hypertensive crisis I guess this is the risk I am willing to take.
Some research states that pain and palpitations are a "normal" side effect of taking parnate whereas other sources state that you should tell you should immediately tell your doctor if you do experience these. In any case, some sources state that doctors should not rely on blood pressure to see if you are in hypertensive crisis as you could be as a result of hypotension. I just don't understand how sometimes you can have hypotension and sometimes you can have severe hypotension.
I also found the stimulant effect wear off in about 2-3hours and replaced with severe restlessness (I think this is akathsia)and I would have to shake my leg so much that I could actually get up in the morning and go for a run to shake off all the energy. When I am on it, I get 3-4 hours sleep at most but I force myself to try and get 8 hours even though I never fall into REM or deep sleep when I am on it.
To me it feels like I have been to the gym when I have not. Now that I am back at university after my summer break I hope it can do the same the ability to increase concentration levels.
I am not sure if my pupils become dilated as when I shine my lap and look in the mirror they shrink really small.
I am glad that your pdoc pulled the plug on you.Did you tell him you developed a tolerance to it? I get mine from a medical centre with a few GP's and I basically go in and ask for a script and they give it too me no questions asked. I guess in those kinds of practices the main aim is to turn over patients in 5 minutes, thats how they make money.
Britney
Posted by Larry Hoover on March 30, 2008, at 13:55:29
In reply to Re: Parnate metabolites, posted by Britney27 on March 28, 2008, at 21:36:55
I am very uncomfortable with tone of this thread. This drug is nearly 50 years old, and was never rigorously tested, like all newer drugs are. Even the tyramine-induced adverse reaction connection was not so much as suggested until 10 years after the drug was made available. The literature is nearly devoid of reliable systematic investigation about this drug. I've spent some time researching it, and this is my best summary.
First off, true addiction to antidepressants is a rare phenomenon, but more than 75% of the literature cases reported are of tranylcypromine addiction. I fear that's what I'm looking at here. It is no mistake that the structure of tranylcypromine is similar to amphetamine. That was an intentional act. However, the stimulant activity should be considered to be distinct from the antidepressant activity, in that tolerance to the former quite quickly develops.
I find no evidence that tranylcypromine metabolizes to amphetamine, and most certainly does not metabolize to methamphetamine. Any autopsy findings which reveal the latter two substances must arise from coingestion. Toxic consequences most certainly might arise from foolhardy intake of bioactive amines while tranylcypromine is messing with your enzymes. Yes, tranylcypromine does more than just mess with MAO. Enzymes plural.
The high doses being discussed in this thread are, IMHO, foolhardy. Chasing the stimulant effect through dose increases inevitably endangers life, as the toxic effect threshold does not similarly increase. You'll just stumble across that intersection, and the only thing that might save you is intensive medical support.
Withdrawal from high dose tranylcypromine can produce haloperidol-resistant hallucinations. High dose tranycylpromine can produce thrombocytopenia (loss of blood clotting), and hyperpyrexia (temperature spike). I wouldn't risk those consequences for anything.
Lar
Posted by Quintal on March 30, 2008, at 16:14:29
In reply to Re: Parnate metabolites » Britney27, posted by Larry Hoover on March 30, 2008, at 13:55:29
I'm not sure what to make of the tone of your own post Larry... People regularly post of high-dose parnate use, in fact it's quite rare to hear of a long-term user taking a dose within the recommeneded UK limit of 30mg, and I've remarked on this before. Still, I don't remember anyone being repremanded for 'foolhardy' behaviour in the past - indeed most people are prescribed these doses under the supervision of their doctor. As someone who has actually taken it, I don't consider high-dose Parnate any more reckless or foolhardy than combining Nardil with stimulants or TCAs, which we often read about here. Some people only acheive an adequate therapeutic response at higher doses. 30mg only made me feel agitated and suicidal - a dangerous combination as any, while 80-120mg gave me the best response I've ever had to any antidepressant. I'm not personally bothered by addiction. Most of the drugs that have actually worked for me have been addictive.
I think this might be the autopsy report I read a while ago:
__________________________________________________1: Forensic Sci Int. 1997 Apr 18;86(1-2):103-8.Click here to read Links
The GCMS analysis of tranylcypromine (Parnate) in a suspected overdose.
Crifasi J, Long C.Saint Louis University Medical School, Department of Pathology, Berkeley, Missouri 63134, USA.
A fatal overdose involving tranylcypromine (Parnate) where blood, urine and tissues were quantitated using a pentafluoroproprionic anhydride (PFPA) derivative and gas-chromatography/mass spectroscopy (GCMS). The samples were re-quantified over several weeks demonstrating a significant loss of drug in tissues but not blood or urine specimens. The urine was positive for methamphetamine which has been a suspected metabolite.
PMID: 9153786 [PubMed - indexed for MEDLINE]
__________________________________________________I did wonder if the victim may have been a methamphetamine user, but the authors seem to lean towards the metabolite theory to account for its presence in the urine. Without more information there's no way of knowing for sure. There were other sources supporting the methamphetamine theory, as well as a study or two finding no amphetamine metabolites. I don't have the energy to weed them all out right now. As you say, Parnate has not been extensively researched and some of the material is contradictory.
>Chasing the stimulant effect through dose increases inevitably endangers life...
I think that's an exaggeration.
>High dose tranycylpromine can produce thrombocytopenia (loss of blood clotting), and hyperpyrexia (temperature spike). I wouldn't risk those consequences for anything.
High dose fish oil and vitamin E can also drastically reduce blood clotting, as I found myself (torrential nosebleeds). I'm not unduly alarmed - sometimes it's worth the risk. I remember Lexapro used to give me pyrexia. I thought it was just one of those things you had to put up with. I had neither of those problems while on high-dose Parnate though.
Q
Posted by Larry Hoover on March 30, 2008, at 16:29:14
In reply to Re: Parnate metabolites, posted by Quintal on March 30, 2008, at 16:14:29
> I'm not sure what to make of the tone of your own post Larry...
I'm scared for posters' safety.
One cannot calculate a safe dose based on LD50. One cannot predict one's own toxic threshold. One can, however, assume that taking doses that are associated with prior mortalities might not be a safe thing to do. Whether or not coingestion of bioactive amines was a contributing factor does not, IMHO, make the situation any more predictable, even if we knew for sure.....The risk is attributable to the irreversible MAOI. And, the risk is indeed dose-dependent. I would argue that if one finds themselves drawn to doses of tranylcypromine that fall within a therapeutic index of two or less, then one is using the wrong drug.
Lar
Posted by Larry Hoover on March 30, 2008, at 16:37:56
In reply to Re: Parnate metabolites, posted by Quintal on March 30, 2008, at 16:14:29
P.S.
With respect to methamphetamine as a potential metabolite of tranylcypromine......
The only way this could arise is if the cyclopropane ring to which the amine group is attached is opened. Two possible products of the ring-opening might arise, one of which is amphetamine, which could potentially serve as a necessary intermediate to methamphetamine. However, intensive metabolic studies have failed to show that either of these two intermediate metabolites are, in fact, produced. Methamphetamine would require the addition of CH5, i.e. a combined methylation/hydrogenation reaction which also opens that same ring, and I know of no reasonable way to effect that reaction, even in the laboratory. If there's no evidence for the production of amphetamine, then methamphetamine production is quite out of the question.
Lar
Posted by Quintal on March 30, 2008, at 16:58:03
In reply to Re: Parnate metabolites » Quintal, posted by Larry Hoover on March 30, 2008, at 16:37:56
> I'm scared for posters' safety.
So that's your primary motive?
> One cannot calculate a safe dose based on LD50. One cannot predict one's own toxic threshold. One can, however, assume that taking doses that are associated with prior mortalities might not be a safe thing to do. Whether or not coingestion of bioactive amines was a contributing factor does not, IMHO, make the situation any more predictable, even if we knew for sure.....The risk is attributable to the irreversible MAOI. And, the risk is indeed dose-dependent. I would argue that if one finds themselves drawn to doses of tranylcypromine that fall within a therapeutic index of two or less, then one is using the wrong drug.
>
> LarWith all due respect, I think it's really for the patient and doctor to decide together whether high-dose Parnate is safe and appropriate in their individual case. Usually by the time people have arrived at MAOIs it's a last-ditch attempt after safer drugs have failed anyway.
>With respect to methamphetamine as a potential metabolite of tranylcypromine......
I have no emotional investment in the methamphetamine metabolite theory whatsoever. If your chemistry is as good as it sounds then I'd say you're probably right. However, there have been a number of reports suggesting methamphetamine and other amphetamine-like metabolites over the years, and I think at least one Parnate user tested positive for amphetamines after being forced to undergo a random drug test at work. I'm not a professional scientist so I'm not going to attempt to dissect all of the possibilities therein.
Q
Posted by Larry Hoover on March 30, 2008, at 17:26:36
In reply to Re: Parnate metabolites » Larry Hoover, posted by Quintal on March 30, 2008, at 16:58:03
> > I'm scared for posters' safety.
>
> So that's your primary motive?Yes.
> I have no emotional investment in the methamphetamine metabolite theory whatsoever. If your chemistry is as good as it sounds then I'd say you're probably right. However, there have been a number of reports suggesting methamphetamine and other amphetamine-like metabolites over the years, and I think at least one Parnate user tested positive for amphetamines after being forced to undergo a random drug test at work. I'm not a professional scientist so I'm not going to attempt to dissect all of the possibilities therein.
Tranylcypromine's structure is not too different from that of amphetamine. See structures at: http://en.wikipedia.org/wiki/Tranylcypromine
and http://en.wikipedia.org/wiki/AmphetamineThe small 'triangle' in the former is the cyclopropane ring. It can open at more than one place, producing the primary or secondary amine. The secondary amine is the more likely product, and is called amphetamine. The similarity in the structures undoubtedly leads to poor resolution during analysis, leading to false positives for amphetamine on screening tests. However, more specific tests have always failed to find amphetamine as a metabolite of tranylcypromine.
As I stated earlier, the structural similarity of tranylcypromine to amphetamine was intentional (according to Goodman and Gillman's 'The Pharmacological Basis of Therapeutics', which is the 'bible' for phsychiatrists and pharmacists, both), in order to confer stimulant activity to the MAOI. Unfortunately, the consequence of that similarity is a vulnerability to true stimulant addiction.
Lar
Posted by Quintal on March 30, 2008, at 18:02:26
In reply to Re: Parnate metabolites » Quintal, posted by Larry Hoover on March 30, 2008, at 17:26:36
>The similarity in the structures undoubtedly leads to poor resolution during analysis, leading to false positives for amphetamine on screening tests. However, more specific tests have always failed to find amphetamine as a metabolite of tranylcypromine.
Well there's one here that detected amphetamine, methamphetamine and PEA by gas chromatography in the plasma of another Parnate overdose. It says their identity was confirmed by mass spectrometry.
__________________________________________________1: Psychol Med. 1979 May;9(2):377-82.Links
Tranylcypromine ('Parnate') overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma.
Youdim MB, Aronson JK, Blau K, Green AR, Grahame-Smith DG.A case of tranylcypromine overdose is reported. Tranylcypromine, amphetamine methamphetamine and phenylethylamine were detected in the plasma by gas chromatography and their identity confirmed by mass spectrometry. The data suggested that the amphetamines were metabolic products of tranylcypromine. Platelet monoamine oxidase activity was more than 95% inhibited during the 72 h after the overdose despite complete clinical recovery by that time. The possible role of amphetamines and phenylethylamine in causing the clinical manifestations of tranylcypromine overdose is discussed.
PMID: 472083 [PubMed - indexed for MEDLINE]
__________________________________________________It seems unlikely that anyone would be taking amphetamine, methamphetamine and phenylethylamine all at the same time with Parnate on board, and this is the second report I've found that has detected methamphetamine in a Parnate overdose. I also found a report of another two Parnate overdoses where no amphetamine metabolites had been detected. It's always possible that the metabolites were there, but the tests failed to detect them for some reason. Maybe some people metabolize Parnate differently? I don't know.
__________________________________________________1: J Anal Toxicol. 1996 Sep;20(5):301-4.Links
One fatal and one nonfatal intoxication with tranylcypromine. Absence of amphetamines as metabolites.
Iwersen S, Schmoldt A.Department of Legal Medicine, University of Hamburg, Germany.
Two very different cases of overdose with tranylcypromine are presented. One clinical case involving the ingestion of 400 mg tranylcypromine with suicidal intention and one fatality with a suspicion of possible tranylcypromine overdose were examined. Both cases showed similar blood concentrations (0.5 and 0.7 mg/L, respectively), but the clinical case exhibited only mild symptoms of intoxication. The fatality showed no other drugs that could provide an explanation for the death of a 40-year-old male except tranylcypromine. Consideration of the drug concentrations in the fatality in relation to the case findings and other reported data indicates the tranylcypromine overdose as the probable cause of death, despite the low blood concentration. In addition, we looked for evidence of amphetamine as a putative metabolite in both cases. No amphetamines were detected in the overdose cases reported here.
PMID: 8872238 [PubMed - indexed for MEDLINE]
__________________________________________________>As I stated earlier, the structural similarity of tranylcypromine to amphetamine was intentional (according to Goodman and Gillman's 'The Pharmacological Basis of Therapeutics', which is the 'bible' for phsychiatrists and pharmacists, both), in order to confer stimulant activity to the MAOI.
Are you saying tranylcypromine may have stimulant properties in itself?
Q
Posted by undopaminergic on March 30, 2008, at 18:15:46
In reply to Re: Parnate metabolites » Larry Hoover, posted by Quintal on March 30, 2008, at 16:58:03
Most attempts to investigate the metabolism of tranylcypromine in humans have failed to detect amphetmines as metabolites. However, it appears that the studies have included only a very small number of subjects, and that the doses used have been rather low. It is possible that a massive dose would result in intestinal and hepatic concentrations of tranylcypromine that are sufficient to activate metabolic pathways that are not involved in the breakdown of the drug at low concentrations. Furthermore, differences in digestive flora (bacteria, fungi) may result in differences in the range of compounds formed from the same starting material in different individuals.
On the other hand, amphetamines as tranylcypromine metabolites may well be only a myth that is sufficiently plausible so as not to be easily dismissed.
There are also alternative hypothetical explanations for the apparently unique properties of tranylcypromine (as a particularly addictive antidepressant, etc.). For example, the stimulant effects may result not from amphetamines, but from other active metabolites or from tranylcypromine itself. I don't know if it has been investigated, but tranylcypromine might function as a dopamine (or multiple monoamine) reuptake inhibitor (like cocaine and methylphenidate) or neurotransmitter-releasing agent (like amphetamine). Such effects may become pronounced only at high doses, which may explain the lack of stimulant-like properties of the drug at low doses.
As to toxicity, even if data from rats were applicable to humans, one can't compare data on acute toxicity, such as a single massive dose in a tranylcypromine-naive animal, to a case of slow titration over a long period of time. Not even the data from cases of overdose in humans are necessarily applicable, as they generally describe situations of a drastic, large and sudden increase in dose (suicide attempts, etc.). Chronic toxicity is relevant, but there is not much information available on the long-term effects of tranylcypromine or other MAOIs, except anecdotal reports of apparent safe and effective use. It is more than likely that, by slow titration, one may surpass doses that would be lethal to a trancylcypromine-naive individual - as an exmaple, here is a report of a daily dose of 440 mg:
http://www.ncbi.nlm.nih.gov/pubmed/1873639Anyway, even if the body is given time to adjust to ever increasing doses of tranylcypromine, the increases must eventually come to an end - in one way or the other. At this time, the factors that ultimately limit dose escalation do not seem well (if at all) defined, so it is up to adventurous users to explore them, and hopefully document and publish their findings.
Go forward in thread:
Psycho-Babble Neurotransmitters | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.