I have a question about Tyramine.

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Eric01

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http://en.wikipedia.org/wiki/Tyramine

Say one wanted to make a pill to degrade most (if not all) Tyramine in a person's stomach to Octopamine

http://en.wikipedia.org/wiki/Octopamine

The only difference in chemical structure between the two is a hydroxide group on the secondary carbon.

Would it be feasible to design a drug that is safe for a human user and that could do simple substitution reactions on the secondary carbon of Tyramine with a hydroxide nucleophile?

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Would it be feasible to design a drug that is safe for a human user and that could do simple substitution reactions on the secondary carbon of Tyramine with a hydroxide nucleophile?

Any small molecule drug that will oxidize tyramine monomer in your stomach is going to kill you if such a drug even exists
 
Any small molecule drug that will oxidize tyramine monomer in your stomach is going to kill you if such a drug even exists

Would there be any way to oxidize tyramine safely?
 
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Yes, there would be!


Well my idea is that currently Nardil is indicated as the most effective treatment for major depression and social anxiety disorder. However, the vulnerability it permits to tyramine makes it so few prescribe it.

My idea would be to design a drug that would oxidize tyramine into opamine, which would then reduce pressor response instead of increasing pressor response leading to hypertensive crisis.

Therefore patients could take Nardil, and an additional drug to take away tyramine risks and be happy.
 
Well you'd still be left with all the drug interactions, which are the real reason we don't use Nardil and other MAO-I's for depression anymore. That and the ability to kill yourself pretty efficiently with an intentional overdose.
 
Well my idea is that currently Nardil is indicated as the most effective treatment for major depression and social anxiety disorder. However, the vulnerability it permits to tyramine makes it so few prescribe it.

My idea would be to design a drug that would oxidize tyramine into opamine, which would then reduce pressor response instead of increasing pressor response leading to hypertensive crisis.

Therefore patients could take Nardil, and an additional drug to take away tyramine risks and be happy.

Yes, it was obvious where you were going with it. Would large doses of octopamine in an MAOI treated patient be safe? Is there data to suggest this would result in less AE than tyramine itself?
 
Well octopamine does not activate alpha or beta adrenergic receptors. In addition octopamine is packed into the synaptic vesicles, displacing noepiniphrine, reducing the amount of noepiniphrine that can be secreted into the synapses to cause a hypertensive crisis.

Theoretically it makes sense. I've not been able to locate trials to demonstrate evidence of it working on humans.

Any way I could experiment with it? I have a college degree!! (FDA probably not impressed.)
 
Well you'd still be left with all the drug interactions, which are the real reason we don't use Nardil and other MAO-I's for depression anymore. That and the ability to kill yourself pretty efficiently with an intentional overdose.


To be frank, people are taking this drug anyways, having either mental disorder is barely living in and of itself. There's no reason to deny many people an opportunity to live a life they want because of a few people who're irresponsible.

Currently there's over 50,000 people on Nardil alone in USA. So it is still being used, we should be looking for ways to make MAOI's more viable. Drug interactions are much easier to avoid, i.e. have patients not take any other drug while on the medication. It's the eating that worries most doctors, because patients can't avoid eating.
 
To be frank, people are taking this drug anyways, having either mental disorder is barely living in and of itself. There's no reason to deny many people an opportunity to live a life they want because of a few people who're irresponsible.

Currently there's over 50,000 people on Nardil alone in USA. So it is still being used, we should be looking for ways to make MAOI's more viable. Drug interactions are much easier to avoid, i.e. have patients not take any other drug while on the medication. It's the eating that worries most doctors, because patients can't avoid eating.

Wouldn't the research time and dollars be better spent identifying specific targets instead of using the MAO-I shotgun approach? I don't know too much about neuropharmacology, but I thought theory was leading towards specific receptor targets rather than a generalized neurologic dysfunction.

You're also leaving out the drug interactions inherent to MAO-I's. Those would not be avoided by eliminating the tyramine problem.
 
Wouldn't the research time and dollars be better spent identifying specific targets instead of using the MAO-I shotgun approach? I don't know too much about neuropharmacology, but I thought theory was leading towards specific receptor targets rather than a generalized neurologic dysfunction.

You're also leaving out the drug interactions inherent to MAO-I's. Those would not be avoided by eliminating the tyramine problem.


I mean all of those other things, drug interactions, other possible problems are valid concerns. I'm just wondering if it's just possible to oxidize tyramine in a human safely?
 
I knew a guy taking nardil, he ate a lot of cereal.

:thumbup:

super-cool-story-bro.png
 
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Emsam(tm). Transdermal MAOI which leaves MAO in the gut intact, thus the manufacturer was able to get the food restriction labeling waived and or reduced by the FDA depending on dosing.
 

HA!, sweet picture. It always just stick in my head cause when I'd work Friday nights he'd pick his Nardil and get 3 boxes of cereal (rice krispies, frosted flakes and corn puffs). Didn't help he also had crazy Albert Einstein hair and he was the ONLY person in our 2500rx/week pharmacy getting it
 
Emsam(tm). Transdermal MAOI which leaves MAO in the gut intact, thus the manufacturer was able to get the food restriction labeling waived and or reduced by the FDA depending on dosing.

It'd be nice if they made a transdermal Nardil approved at high dosages. Often with psychiatric medicine you have to be able to reach a certain threshold dosage before therapeutic effects kick in.


EDIT: If I had a prescription for Nardil, would a pharmacist be able to convert the pill form into a transdermal patch?
 
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It'd be nice if they made a transdermal Nardil approved at high dosages. Often with psychiatric medicine you have to be able to reach a certain threshold dosage before therapeutic effects kick in.


EDIT: If I had a prescription for Nardil, would a pharmacist be able to convert the pill form into a transdermal patch?

Do you think phenelzine has the proper physiochemical properties to be administered transdermally?

and I think selegiline's lack of food interaction is more due to it's selectiveness than the lack of gut exposure when given transdermally
 
Do you think phenelzine has the proper physiochemical properties to be administered transdermally?

and I think selegiline's lack of food interaction is more due to it's selectiveness than the lack of gut exposure when given transdermally

My question was more about legality than actuality. However now im curious say it does have the proper physiochemical properties to be administered transdermally..could a pharmacist legally compound my medication into a transdermal patch? I don't presume to know a lot about this stuff but if the lack of food interaction was intrinsic to selegilene then there would have been little reason to pursue patch form. If this does preserve the stomach and small intestines supply of mao enzyme then theoretically this should eliminate dietary concerns
 
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My question was more about legality than actuality. However now im curious say it does have the proper physiochemical properties to be administered transdermally..could a pharmacist legally compound my medication into a transdermal patch? I don't presume to know a lot about this stuff but if the lack of food interaction was intrinsic to selegilene then there would have been little reason to pursue patch form. If this does preserve the stomach and small intestines supply of mao enzyme then theoretically this should eliminate dietary concerns

A pharmacist can legally compound any medication prescribed by a doctor and I can almost guarantee that transdermal phenylazine would have zero effect on gut MAO. You could eat all the cheese and wine you wanted
 
selegiline becomes non-selective at higher doses, which the makers of Emsam found out when they trialed it.. i believe
 
My question was more about legality than actuality. However now im curious say it does have the proper physiochemical properties to be administered transdermally..could a pharmacist legally compound my medication into a transdermal patch? I don't presume to know a lot about this stuff but if the lack of food interaction was intrinsic to selegilene then there would have been little reason to pursue patch form. If this does preserve the stomach and small intestines supply of mao enzyme then theoretically this should eliminate dietary concerns

The lack of food interacton is true for selegiline oral low dose, which has some efficacy for parkinsons, but the manufacturer and researchers theorized and then concluded that the higher dose required to achieve MAO-A inhibition (and presumably antidepressant efficacy alongside) was hazardous, food wise. Thus the patch. (I did a presentation on this drug, as it's one of my favorite 'cool examples of pharmaceutics')

Both phenelzine and selegiline have similar molecular natures, so at first glance comparing the molecules, one would think phenelzine would be capable of being delivered transdermally, but, , as they say, 'in vivo' the picture may be different. I would talk to a pharmaceutics professor at your university. I bet they'd be able to give you a much more definite answer.
 
Both phenelzine and selegiline have similar molecular natures, so at first glance comparing the molecules, one would think phenelzine would be capable of being delivered transdermally, but, , as they say, 'in vivo' the picture may be different.
take a look at the logP for each. phenelzine is quite hydrophylic
 
take a look at the logP for each. phenelzine is quite hydrophylic

yeah i realized this like 10 minutes after posting. good catch! i meant structures, visually at a glance. hehe 'natures' is going a bit too far. i'd say to the op to recommend selegiline transdermal (to the patient of course, since it is discouraged to ask for personal medical advice) in this situation then rather than face the potential roadblock of transdermal hydrophilic drugs. Personally I tried selegiline when I had some depression a while back and it was pretty damn cool. One other nice thing about it compared to the SSRI class or TCA class is that taper-off can be accomplished with the help of the enzymes half lives themselves (40-50 ish days i believe), since the drug basically is a suicide substrate (heh heh, pardon the pun since we are dealing with the topic of antidepressants, oops)
 
If one just forgets the transdermal approach method, and instead elects for an injectable version. Would that have the advantage of bypassing the gut + small intestine, while also not having the disadvantage of only being able to put in a small dose + worry about skin absorption?
 
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