demitriden
Greenlighter
- Joined
- Jan 12, 2009
- Messages
- 24
I know there are many individuals on this site that have greater understanding of neurology and psychopharmacology than I, and I wish to ask these people for their hypothesis.
Here is the given scenario. You can think of it as a hypothetical one if it helps, since the particular elements of it are not subject to debate.
In any event, here it is:
-Person X ("Px") has been dosing with piracetam and huperzine-a consistently at responsible doses (ie. no abuse).
-Px starts to experience one side-effect #1--odd, loud, moderate in frequency stomach/digestive noises.
-SD#1 was troubling enough for Px to decide to halt dosing altogether.
-2-3 days after the day Px decided to quit the noots, SD#2 begins--minor, involuntary, frequent, random muscle tics or convulsions. [wondering if the events correlated? did SD#2 begin because Px stopped dosing?]
-3 weeks later, SD#1 diminishes and is completely gone. However in the same week, Px begins to suffer from SD#3--debilitating, unrelenting, severe, chronic pain.
-Px suffers from SD#2 and SD#3 for the next 6-7 months. SD#3 is particularly serious and takes a toll on Px. SD#3's chronic pain induces night-time insomnia and day-time lethargy for Px. This vicious cycle causes Px flooding of stress.
-Friends of Px light-heartedly fun of him, though to him it is not an issue to be taken lightly. Px's friends joke saying noots have helped him developed superpowers to perceive pain in a heighten level relative to normal people.
-Suffering continues. Px kept telling himself that SD#3's serverity would subside in time. It doesn't. Suffering continues and his spirit is absolutely gone. At Px's breaking point, Px finally seeks medical help. He had not before because he could not afford it. In fact, he still can't. Nevertheless, as a last resort, he decides to go and get evaluated.
-Px first talks to a psychologist, then is referred to a psychiatrist. Px is ordered to take various blood tests, but no irregularities can be found.
-Px has become very depressed because of the chronic heightened sense of pain and the psychiatrist realizes this. Psych prescribes Px an anti-depressant, Paxil (paroxentine). Px is pessimistic that Paxil would help much and Px is hesitant to take it because Px had heard horror stories about Paxil. In any event, as time passes, to Px's suprise, Paxil has helped him in many aspects of his life. He feels less depressed, more spirited, more energized, is able to sleep better, fall asleep easier, concentrate more. Additionally, his chronic pain he had been suffering from declines. On a scale of 1-10 before Paxil, pain was lvl. 7; however after Paxil, somatic pain is now a 5.
-Px goes to Psych and complains about sexual dysfunction. Psych prescribes Wellbutrin to mediate this relatively minor dilemma, compared to the severe level of somatic pain he had before. 150mg Wellbutrin XL is given to Px; Psych says this is the lowest dose. To his amazement, the NRDI atypical depressant Wellbutrin relieves him of SD#4!!! With only Paxil pain lvl. decreases by 2, from 7 to 5. But with Wellbutrin pain lvl. reduces two-fold, from 5 to 1. Pain is still present, but now very subtle. Px is almost back to himself.
Okay so that's the scenario. Again, the particular facts of it are not subject to debate so think of this as a hypothetical one if it helps.
My own hypothesis: Piracetam and huperzine-a totally F'ed up Px's equilibrium some how. This part I'm not sure how! Nevertheless, it's a given fact in the scenario that is irrefutable. Someone take a stab please. What I do know is that Wellbutrin is classified as an aminoketone antidepressant. Its mechanism of action is thought to be via dual inhibition of norepinephrine and dopamine reuptake (NDRI) without clinically significant serotonin reuptake inhibition (Horst and Preskorn 1998; Stahl et al. 2004). Itself has weak reuptake properties for dopamine, and weaker yet reuptake properties for norepinephrine. The action of the drug on norepinephrine and dopamine neurotransmission, however, has always appeared to be more powerful than these weak properties could explain, which has led to proposals that bupropion acts rather vaguely as an adrenergic modulator of some type. I'm wondering if this element has something to do with Px's recovery. It also acts as an antagonist to nicotinic acetylcholine (nACh) receptors, which I also think may be relevant.
Significantly, although other antidepressants often produce their effects by downregulation of the postsynaptic noradrenergic receptors, bupropion differs in how it interacts with noradrenergic systems in that it decreases the firing rate of neurons in the locus coeruleus in a dose-dependent manner (B. R. Cooper et al. 1994; T. B. Cooper et al. 1984). Maybe this has something to do with the reduction in in lvl. of pain perception? Anyway, studies have shown that acute administration of bupropion not only decreases firing of brain stem NE and DA neurons but also increases extracellular NE and DA concentrations in the nucleus accumbens (Fava et al. 2005).
Another hypothesis is that Wellbutrin and Paxil somehow works synergistically to overcome a threshold of pain relief that neither of the two, especially Paxil, could have done by itself (I'm less convinced of this for some reason, but please give me your input).
Another hypothesis is that since Paxil is a inhibitor and substrate of the liver enzyme CYP 2D6 and Wellbutrin is also uses this enzyme to metabolize, Px's blood plasma level of Wellbutrin, even though it's at its lowest dose of 150mg XL, is drastically potentiated.
I'm not at all familiar pharmacokinetics, disposition or mechanism of action of piracetam or huperzine-a. Can anyone help me piece this mystery together?
Here is the given scenario. You can think of it as a hypothetical one if it helps, since the particular elements of it are not subject to debate.
In any event, here it is:
-Person X ("Px") has been dosing with piracetam and huperzine-a consistently at responsible doses (ie. no abuse).
-Px starts to experience one side-effect #1--odd, loud, moderate in frequency stomach/digestive noises.
-SD#1 was troubling enough for Px to decide to halt dosing altogether.
-2-3 days after the day Px decided to quit the noots, SD#2 begins--minor, involuntary, frequent, random muscle tics or convulsions. [wondering if the events correlated? did SD#2 begin because Px stopped dosing?]
-3 weeks later, SD#1 diminishes and is completely gone. However in the same week, Px begins to suffer from SD#3--debilitating, unrelenting, severe, chronic pain.
-Px suffers from SD#2 and SD#3 for the next 6-7 months. SD#3 is particularly serious and takes a toll on Px. SD#3's chronic pain induces night-time insomnia and day-time lethargy for Px. This vicious cycle causes Px flooding of stress.
-Friends of Px light-heartedly fun of him, though to him it is not an issue to be taken lightly. Px's friends joke saying noots have helped him developed superpowers to perceive pain in a heighten level relative to normal people.
-Suffering continues. Px kept telling himself that SD#3's serverity would subside in time. It doesn't. Suffering continues and his spirit is absolutely gone. At Px's breaking point, Px finally seeks medical help. He had not before because he could not afford it. In fact, he still can't. Nevertheless, as a last resort, he decides to go and get evaluated.
-Px first talks to a psychologist, then is referred to a psychiatrist. Px is ordered to take various blood tests, but no irregularities can be found.
-Px has become very depressed because of the chronic heightened sense of pain and the psychiatrist realizes this. Psych prescribes Px an anti-depressant, Paxil (paroxentine). Px is pessimistic that Paxil would help much and Px is hesitant to take it because Px had heard horror stories about Paxil. In any event, as time passes, to Px's suprise, Paxil has helped him in many aspects of his life. He feels less depressed, more spirited, more energized, is able to sleep better, fall asleep easier, concentrate more. Additionally, his chronic pain he had been suffering from declines. On a scale of 1-10 before Paxil, pain was lvl. 7; however after Paxil, somatic pain is now a 5.
-Px goes to Psych and complains about sexual dysfunction. Psych prescribes Wellbutrin to mediate this relatively minor dilemma, compared to the severe level of somatic pain he had before. 150mg Wellbutrin XL is given to Px; Psych says this is the lowest dose. To his amazement, the NRDI atypical depressant Wellbutrin relieves him of SD#4!!! With only Paxil pain lvl. decreases by 2, from 7 to 5. But with Wellbutrin pain lvl. reduces two-fold, from 5 to 1. Pain is still present, but now very subtle. Px is almost back to himself.
Okay so that's the scenario. Again, the particular facts of it are not subject to debate so think of this as a hypothetical one if it helps.
My own hypothesis: Piracetam and huperzine-a totally F'ed up Px's equilibrium some how. This part I'm not sure how! Nevertheless, it's a given fact in the scenario that is irrefutable. Someone take a stab please. What I do know is that Wellbutrin is classified as an aminoketone antidepressant. Its mechanism of action is thought to be via dual inhibition of norepinephrine and dopamine reuptake (NDRI) without clinically significant serotonin reuptake inhibition (Horst and Preskorn 1998; Stahl et al. 2004). Itself has weak reuptake properties for dopamine, and weaker yet reuptake properties for norepinephrine. The action of the drug on norepinephrine and dopamine neurotransmission, however, has always appeared to be more powerful than these weak properties could explain, which has led to proposals that bupropion acts rather vaguely as an adrenergic modulator of some type. I'm wondering if this element has something to do with Px's recovery. It also acts as an antagonist to nicotinic acetylcholine (nACh) receptors, which I also think may be relevant.
Significantly, although other antidepressants often produce their effects by downregulation of the postsynaptic noradrenergic receptors, bupropion differs in how it interacts with noradrenergic systems in that it decreases the firing rate of neurons in the locus coeruleus in a dose-dependent manner (B. R. Cooper et al. 1994; T. B. Cooper et al. 1984). Maybe this has something to do with the reduction in in lvl. of pain perception? Anyway, studies have shown that acute administration of bupropion not only decreases firing of brain stem NE and DA neurons but also increases extracellular NE and DA concentrations in the nucleus accumbens (Fava et al. 2005).
Another hypothesis is that Wellbutrin and Paxil somehow works synergistically to overcome a threshold of pain relief that neither of the two, especially Paxil, could have done by itself (I'm less convinced of this for some reason, but please give me your input).
Another hypothesis is that since Paxil is a inhibitor and substrate of the liver enzyme CYP 2D6 and Wellbutrin is also uses this enzyme to metabolize, Px's blood plasma level of Wellbutrin, even though it's at its lowest dose of 150mg XL, is drastically potentiated.
I'm not at all familiar pharmacokinetics, disposition or mechanism of action of piracetam or huperzine-a. Can anyone help me piece this mystery together?
