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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 falconman on April 13, 2007, at 7:53:12
Does the fact that we break this chemical down so quickly signify that its maybe toxic? Could it be an evolutionary self-protection mechanism that serves an important purpose? If you take low dose deprenyl(selegeline) and DL-phenylalanine together, to increase production and reduce its break down; could you possibly be playing with fire?
Thanks
Posted by Larry Hoover on April 13, 2007, at 9:28:44
In reply to Is phenylethylamine neurotoxic?, posted by falconman on April 13, 2007, at 7:53:12
> Does the fact that we break this chemical down so quickly signify that its maybe toxic?
No. Not that I know of.
> Could it be an evolutionary self-protection mechanism that serves an important purpose?
More of a signal control mechanism. Cells communicate, but the idea is to limit the time course of the signal, so that there is a real-time responsivity within the system. Quick degradation "cleans up the mess".
> If you take low dose deprenyl(selegeline) and DL-phenylalanine together, to increase production and reduce its break down; could you possibly be playing with fire?
> ThanksThe only fire aspect would be that changes in receptor function might occur, as an adaptive mechanism. For many functions where we try to play around with natural processes by manipulating e.g. precursors, we find that the initial responsivity dampens over time. That's because Mama Nature has feedback regulatory systems embedded all over the place, is all.
To maintain overt physiological response over time, it's probably best to go with p.r.n. dosing of the phenylalanine, in this example. Take it as needed, and try to avoid changes in the responsivity of the system. You do not want it to learn to accommodate the exogenous source, but to remain "hungry" for the signal you seek. Holidays from exposure serve a similar function. You can only learn how this works for you by experimentation.
Lar
Posted by falconman on April 13, 2007, at 9:42:59
In reply to Re: Is phenylethylamine neurotoxic? » falconman, posted by Larry Hoover on April 13, 2007, at 9:28:44
Posted by falconman on April 13, 2007, at 9:54:03
In reply to Re: Is phenylethylamine neurotoxic? » falconman, posted by Larry Hoover on April 13, 2007, at 9:28:44
If feedback regulatory systems are everywhere, surely all drugs would 'poop out'? How come evan without 'drug/medication holidays' many don't? Just a thought.
> > Does the fact that we break this chemical down so quickly signify that its maybe toxic?
>
> No. Not that I know of.
>
> > Could it be an evolutionary self-protection mechanism that serves an important purpose?
>
> More of a signal control mechanism. Cells communicate, but the idea is to limit the time course of the signal, so that there is a real-time responsivity within the system. Quick degradation "cleans up the mess".
>
> > If you take low dose deprenyl(selegeline) and DL-phenylalanine together, to increase production and reduce its break down; could you possibly be playing with fire?
> > Thanks
>
> The only fire aspect would be that changes in receptor function might occur, as an adaptive mechanism. For many functions where we try to play around with natural processes by manipulating e.g. precursors, we find that the initial responsivity dampens over time. That's because Mama Nature has feedback regulatory systems embedded all over the place, is all.
>
> To maintain overt physiological response over time, it's probably best to go with p.r.n. dosing of the phenylalanine, in this example. Take it as needed, and try to avoid changes in the responsivity of the system. You do not want it to learn to accommodate the exogenous source, but to remain "hungry" for the signal you seek. Holidays from exposure serve a similar function. You can only learn how this works for you by experimentation.
>
> Lar
Posted by linkadge on April 14, 2007, at 9:39:31
In reply to Re: Is phenylethylamine neurotoxic? » Larry Hoover, posted by falconman on April 13, 2007, at 9:54:03
Possably.
Linkadge
Posted by Larry Hoover on April 14, 2007, at 10:09:36
In reply to Re: Is phenylethylamine neurotoxic? » Larry Hoover, posted by falconman on April 13, 2007, at 9:54:03
> If feedback regulatory systems are everywhere, surely all drugs would 'poop out'? How come evan without 'drug/medication holidays' many don't? Just a thought.
One of the distinctive aspects of what I think of when I think of "drug" is the unnaturalness of the molecule, from an endogenous/exogenous perspective. A substance obtains the quality of being a drug by being outside the regulatory framework. That's not to say that regulatory processes cannot be activated in response to exposure, but that initial effects are due precisely to the foreigness.
Rather than supposing that drug poop out is an either/or situation, I perceive it as time-dependent. Given enough time, I'd expect every drug to poop out, eventually. The limit, of course, is infinite time, and nobody lives forever. But within lifespans of a population, some individuals will poop out after much shorter intervals of time than others. If observed for long enough, the incidence of poop out within the exposed population would rise towards 100%. Before it reaches 100%, some lucky folk simply haven't pooped out....yet.
Remember, I'm only suggesting a model. There are exceptions to everything that humans can imagine. The distinction between drugs and endogenous molecules is arbitrary; niacin is considered a drug at supra-physiological dosing.... Etc. Etc.
Lar
Posted by linkadge on April 14, 2007, at 11:02:15
In reply to Re: Is phenylethylamine neurotoxic? » falconman, posted by Larry Hoover on April 14, 2007, at 10:09:36
I am guessing that a drug is more likely to poop out depending on the degree of which it brings a person closer to or farther from normalacy.
For instance, if a drug is making a person high, then there will be a strong oppositional force instituted by the brain to counteract the drug.
If, however, a drug brings a person closer to a normal state of mind, I would think the brain is less likely to reject it.
Most people best remember the extreme states of emotion, and less so the normal states of emotion. So, poopout could be defined a number of
ways including the transition from a high state
to a normal state of mind.Linkadge
Posted by falconman on April 14, 2007, at 11:11:49
In reply to Re: Is phenylethylamine neurotoxic? » falconman, posted by Larry Hoover on April 14, 2007, at 10:09:36
> > If feedback regulatory systems are everywhere, surely all drugs would 'poop out'? How come evan without 'drug/medication holidays' many don't? Just a thought.
>
> One of the distinctive aspects of what I think of when I think of "drug" is the unnaturalness of the molecule, from an endogenous/exogenous perspective. A substance obtains the quality of being a drug by being outside the regulatory framework. That's not to say that regulatory processes cannot be activated in response to exposure, but that initial effects are due precisely to the foreigness.
>
> Rather than supposing that drug poop out is an either/or situation, I perceive it as time-dependent. Given enough time, I'd expect every drug to poop out, eventually. The limit, of course, is infinite time, and nobody lives forever. But within lifespans of a population, some individuals will poop out after much shorter intervals of time than others. If observed for long enough, the incidence of poop out within the exposed population would rise towards 100%. Before it reaches 100%, some lucky folk simply haven't pooped out....yet.
>
> Remember, I'm only suggesting a model. There are exceptions to everything that humans can imagine. The distinction between drugs and endogenous molecules is arbitrary; niacin is considered a drug at supra-physiological dosing.... Etc. Etc.
>
> LarObviously between individuals there are huge variables to consider; but within one individuals bio-chemical environment, are you suggesting that the length of time that a med stays effective is directly proportional to the amount it structurally differs (on a molecular level) to the particular endogenous chemical that it resembles or that it is linked to in some way? If it is structurally very similar (or evan identical as in the case of some steroids for example) its effects are likely to be more prolonged than if its 'more foreign', and in this case feedback mechanisms/receptor alterations are brought into play much more rapidly?
I'm sure there are no hard fast rules for any of this. There's probably a different set of rules for different endogenous chemicals, which are dependant upon the unique 'mechanical systems' that they are a part of.
I'm going round in circles now, probably the beer. Man utd vs Watford FA cup semi-final on its way. Don't feel you have to reply I just find this exremely interesting.
Cheers
Posted by Larry Hoover on April 14, 2007, at 13:08:06
In reply to Re: Is phenylethylamine neurotoxic? » Larry Hoover, posted by falconman on April 14, 2007, at 11:11:49
> Obviously between individuals there are huge variables to consider; but within one individuals bio-chemical environment, are you suggesting that the length of time that a med stays effective is directly proportional to the amount it structurally differs (on a molecular level) to the particular endogenous chemical that it resembles or that it is linked to in some way?
No, nothing like that. If the change is in a single atom, it can make a bioactive substance resistant to breakdown, for example, substantially increasing its activity. In contrast, some drugs have powerful effects that we simply cannot yet relate to structure, as they differ so much from the natural substance that they somehow mimic that we see no relationship whatsoever. There are structure/property relationships that we can predict, but there are some properties that we cannot yet relate to structure despite substantial efforts. And I meant this time-dependency thing to be a population variable; a statistic.
For an individual, a drug poops out or it doesn't, and it does so one time only. It's a binary system, with an observable state. Populations, on the other hand, exhibit incidence rates.
Foreign-ness I meant in a vague way. We've created chemicals not seen in nature. We also use chemicals as drugs which are rarely seen in food, but can be found in nature.
> If it is structurally very similar (or evan identical as in the case of some steroids for example) its effects are likely to be more prolonged than if its 'more foreign', and in this case feedback mechanisms/receptor alterations are brought into play much more rapidly?
Steroid drugs can cross the line in my definition, just like I mentioned for niacin, as both are endogenous. Dose/intent then becomes the issue, not the substance per se.
Hormones (or essential nutrients) at physiological doses (i.e. within normal range for a healthy person) would normalize feedback, in turn. The further from physiological one pushes the dose, the greater the feedback resistance. Of course, we can totally overwhelm the body's capacity to regulate a system via feedback, which would bring the *use* more in line with my definition of drug.
> I'm sure there are no hard fast rules for any of this. There's probably a different set of rules for different endogenous chemicals, which are dependant upon the unique 'mechanical systems' that they are a part of.
Getting back to phenylethylamine/phenylalanine, that's why I first raised the issue of discontinuous use, because the rules of that system would work against continuing efficacy from chronic supplementation. An individual might find phenylethylamine to be neurotoxic, despite population evidence that it is not. Both can be true, at the same time. Neither one invalidates the other.
One could argue that one might have phenylethylamine deficiency, from deficiency of the precursor. Or, phenylethylamine resistance, resulting from adaptive responses to normal amounts of PEA. I consider the argument moot, if the point is to feel the difference from ingesting some phenylalanine. I purposely sidestep considering what is "normal", in the first place. Normal, too, is arbitrary, and depends on all kinds of assumptions.
> I'm going round in circles now, probably the beer.
What circles? There are conditions upon which a statement holds true, and others upon which it is false. Questioning the conditions of the argument is precisely what is required to comprehend the nuances of meaning.
> Man utd vs Watford FA cup semi-final on its way. Don't feel you have to reply I just find this exremely interesting.
> CheersI hope you enjoy the game, with or without exogenous phenylalanine. Exogenous ethanol already in good supply... ;-)
Lar
Posted by falconman on April 14, 2007, at 16:20:30
In reply to Re: Is phenylethylamine neurotoxic? » falconman, posted by Larry Hoover on April 14, 2007, at 13:08:06
This is the end of the thread.
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