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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by DSCH on August 11, 2003, at 3:59:53
In tracking down information on future drugs aimed at ADD/ADHD, I came across Perceptin, which was being persued by Gliatech until it seems trouble with class-action litigation and the FDA over their post-surgical adhesion control gel ADCON-L sank the company.
Perceptin, "GT-2331", is a selective H3 receptor antagonist. (For a peak at the molecule, go here... http://www.albmolecular.com/features/tekreps/vol03/no25/ and scroll down a bit).
Bring up histamine, and I immediately have a lot of things to say about it, having gone through extensive allergy shot therapy as a kid. I commonly took the OTC anti-histamine Chlortrimeton which is chlorpheniramine, an H1 antagonist. I have felt seriously awful the few times I have taken Benedryl, which is diphenhydramine and another H1 antagonist. Well, my allergy attacks tapered off with time, though I still have them on occasion usually late at night starting with diarrhea before the bronchial constriction and nasal congestion kick in (food allergy?). More mucking about with Google scared up a number of sites proclaming "Allergic Toxema", "Allergic Tension Fatigue Syndrome", and (shudder) "Chronic Fatigue Immune Dysfunction Syndrome".
Could all this histamine-related activity from allergy attacks, therapy, and medication from when I was young resulted in damage or imbalance that is now reflected with symptoms that lately crop up as hypersomniac depression/ADD?
Is it possible I need more synaptic histamine rather than dopamine, norepinepherine, or serotonin? If so, how do I go about getting it?
Your thoughts, please!
Posted by DSCH on August 11, 2003, at 4:46:12
In reply to Histamine and Hypersomniac Depression/ADD?, posted by DSCH on August 11, 2003, at 3:59:53
Posted by Larry Hoover on August 11, 2003, at 4:54:10
In reply to Histamine and Hypersomniac Depression/ADD?, posted by DSCH on August 11, 2003, at 3:59:53
> In tracking down information on future drugs aimed at ADD/ADHD, I came across Perceptin, which was being persued by Gliatech until it seems trouble with class-action litigation and the FDA over their post-surgical adhesion control gel ADCON-L sank the company.
>
> Perceptin, "GT-2331", is a selective H3 receptor antagonist. (For a peak at the molecule, go here... http://www.albmolecular.com/features/tekreps/vol03/no25/ and scroll down a bit).
>
> Bring up histamine, and I immediately have a lot of things to say about it, having gone through extensive allergy shot therapy as a kid. I commonly took the OTC anti-histamine Chlortrimeton which is chlorpheniramine, an H1 antagonist. I have felt seriously awful the few times I have taken Benedryl, which is diphenhydramine and another H1 antagonist. Well, my allergy attacks tapered off with time, though I still have them on occasion usually late at night starting with diarrhea before the bronchial constriction and nasal congestion kick in (food allergy?).Probably.
>More mucking about with Google scared up a number of sites proclaming "Allergic Toxema", "Allergic Tension Fatigue Syndrome", and (shudder) "Chronic Fatigue Immune Dysfunction Syndrome".
I know it's hard to make the distinction, but there's no way to know if histaminic activity is the cause or the consequence of these syndromes, or if an unseen "third party" is the root problem.
> Could all this histamine-related activity from allergy attacks, therapy, and medication from when I was young resulted in damage or imbalance that is now reflected with symptoms that lately crop up as hypersomniac depression/ADD?My opinion is that I strongly doubt it. More likely, it is merely evidence that you've had a problem for a long time.
> Is it possible I need more synaptic histamine rather than dopamine, norepinepherine, or serotonin?Every drug you mentioned in this thread is an antagonist, a substance that negates the effect of histamine. You'd need less, not more. However, I think that's a simplistic explanation, in any case (just like the serotonin imbalance explanation for depression).
> If so, how do I go about getting it?
>
> Your thoughts, please!The simplest things you can try are the B3-family supplements NADH and niacinamide. The former is implicated in central histamine destruction, while the latter inhibits the release of histamine peripherally. I think that excess histamine reactivity is also related to a deficit in methylation (so-called one-carbon metabolism), so in the longer term, supplementation with methyl donors (B-12 and betaine), along with the other B's (B-complex), and the key minerals zinc and selenium, would be helpful.
Lar
Posted by DSCH on August 11, 2003, at 12:53:20
In reply to Re: Histamine and Hypersomniac Depression/ADD?, posted by Larry Hoover on August 11, 2003, at 4:54:10
> Every drug you mentioned in this thread is an antagonist, a substance that negates the effect of histamine. You'd need less, not more. However, I think that's a simplistic explanation, in any case (just like the serotonin imbalance explanation for depression).
Don't confuse the action of H1 and H3 antagonists. H3 antagonists are not "antihistamines" and cause *more* histamine to be released into the synpases, especially in the posterior hypothalamus. Take a peak at the abstracts you get if you run a search on "H3 antagonist". Activating effects rather than the classic sedation of antihistamines that cross the BBB.
Posted by Zenclearer on August 11, 2003, at 14:29:22
In reply to Re: Histamine and Hypersomniac Depression/ADD?, posted by Larry Hoover on August 11, 2003, at 4:54:10
Regarding methyliation:
Sam-e does this, yes? No one ever mention supplementing stims with Sam-e to offset fatigue.
I've had some success on low Sam-e doses, for short periods; but eventually I get severe GI upset (could be the enteric release?) and I stop the Sam-e.
But I am trying to find a way to offset dex-related fatigue. Even at a low dex dose, I am wiped out more often than not. More only exacerbates the process.
I do take B-complex, zinc, and a good multiple, along with EFAs.
Posted by DSCH on August 11, 2003, at 15:04:55
In reply to Re: Histamine and Hypersomniac Depression/ADD? » Larry Hoover, posted by Zenclearer on August 11, 2003, at 14:29:22
> Regarding methyliation:
>
> Sam-e does this, yes? No one ever mention supplementing stims with Sam-e to offset fatigue.
>
> I've had some success on low Sam-e doses, for short periods; but eventually I get severe GI upset (could be the enteric release?) and I stop the Sam-e.
>
> But I am trying to find a way to offset dex-related fatigue. Even at a low dex dose, I am wiped out more often than not. More only exacerbates the process.
>
> I do take B-complex, zinc, and a good multiple, along with EFAs.Have you tried DLPA? I think it's reduced the side effects from the pemoline I'm taking now, but this has only been for a few days. I'm also taking a time-released B-complex. Could be the dopamine and norepinepherine the dex is knocking on your neurons for isn't available to be released in sufficent quantity in the first place.
Posted by Zenclearer on August 11, 2003, at 15:37:11
In reply to Dexedrine fatigue » Zenclearer, posted by DSCH on August 11, 2003, at 15:04:55
What's DLPA?
Posted by DSCH on August 11, 2003, at 17:21:58
In reply to Re: Dexedrine fatigue » DSCH, posted by Zenclearer on August 11, 2003, at 15:37:11
> What's DLPA?
It is synthetically-made racemic phenylalanine (PA, an amino acid), meaning that it is 50/50 dextrorotatory (D-) and laevorotatory (L-) (i.e. half "left-" and half "right-handed").
L-phenylalanine is the basic building block for dopamine, norepinepherine, and epinepherine. Most of us should be getting plenty of it through our meat-rich American diet but who knows what might be happening in each of us individually?
D-phenylalanine is less common in nature but nevertheless can be converted within the brain to the neurotransmitter beta-phenylethylamine (PEA). I've also read somewhere that D-phenylalanine slows the breakdown of natural endorphins by inhibiting the enzyeme enkephalinase, but I'm not certain I've got that straight at the moment. PEA has been widely bandied about as a "feel good" and stimulating brain agent that gets released in large quantities when we are falling in love with someone. There is a web page swiped from a poster session at a conference that claimed a lab worker who got symptoms of Parkinson's disease after an bio-contaminating lab accident was helped by D-PA. It's in one of my earlier posts (look for "Fantastic Four" in the subject).
You can buy 100% D-PA or 100% L-PA. But why not try dual action and get both? It's cheaper too. The D-PA cannot be used to form the L-monoamines so it doesn't compete with the L-PA for that. A while back 3 Beer Effect posted that the PAs cross the blood brain barrier quite readily which is not true of L-tyrosine (which is the halfway stage between L-PA and L-dopa and has also been recommended as a "brain booster" amino acid suppliment).
Posted by Zenclearer on August 11, 2003, at 18:34:57
In reply to DLPA » Zenclearer, posted by DSCH on August 11, 2003, at 17:21:58
Ah, yes, amino acids. I have tried them. With stims, they cause me elevated BP and effects are very inconsistent, even at 25 mg/day.
I get a rush of positive feeling the first time; then a feeling of severe irritation as it leaves my system the next day. And if I keep taking them, I feel as though my heart is over-stressed (and I exercise and am in good shape).
So alas, they make me feel worse, after the first rush of positive feeling. But likely, yes, there is some deficiency that the stims over-draw from, and I've never found a decent balance.
Further, certain supplements with the stims can cause me severe water retention; it must be tampering with renal hormones, eg, antidiuretic hormone, etc. This of course exacerbates the high BP feeling.
I am a difficult one, indeed!
Posted by DSCH on August 11, 2003, at 18:46:52
In reply to Re: DLPA » DSCH, posted by Zenclearer on August 11, 2003, at 18:34:57
What symptoms prompted your RX of dexedrine in the first place?
Have you experienced going off dexedrine?
Posted by Zenclearer on August 11, 2003, at 18:57:22
In reply to Dexedrine, amino acids, and the heart » Zenclearer, posted by DSCH on August 11, 2003, at 18:46:52
ADHD.
Yes, I have considered many times going off it. In fact, I'm trying to give myself a week off ahead now, and that will be a challenge. But I am sure it's the right thing to do. If nothing else, it will be a break; and I cann assess further after reaching that goal.
Posted by DSCH on August 11, 2003, at 20:09:41
In reply to Re: Dexedrine, amino acids, and the heart » DSCH, posted by Zenclearer on August 11, 2003, at 18:57:22
Since the amino acids clear out fairly quickly, perhaps you could try them out for a few days straight during your "work and drug" holiday if you are able to go ahead with it. It might be that a regimen of vitamins B3, B6, and C plus DLPA could be helpful enough on their own.
If that doesn't do it, perhaps Strattera might be worth a try.
Have you tried "typing" your ADHD symptoms at www.brainplace.com?
Posted by Larry Hoover on August 12, 2003, at 8:28:40
In reply to H1 antagonists vs H3 antagonists, posted by DSCH on August 11, 2003, at 12:53:20
> > Every drug you mentioned in this thread is an antagonist, a substance that negates the effect of histamine. You'd need less, not more. However, I think that's a simplistic explanation, in any case (just like the serotonin imbalance explanation for depression).
>
> Don't confuse the action of H1 and H3 antagonists. H3 antagonists are not "antihistamines" and cause *more* histamine to be released into the synpases, especially in the posterior hypothalamus. Take a peak at the abstracts you get if you run a search on "H3 antagonist". Activating effects rather than the classic sedation of antihistamines that cross the BBB.That's not what this one says:
Ann Pharm Fr. 2003 May;61(3):173-84.
[The histamine H(3) receptor: a target for new drugs][Article in French]
Arrang JM.
Unite de neurobiologie et pharmacologie moleculaire, INSERM U573, Centre Paul Broca, 2ter, rue d'Alesia, F 75014 Paris.
The histamine H3 receptor has been identified in the rat brain as a presynaptic autoreceptor inhibiting histamine synthesis and release. Following its recent cloning, more than fifteen years later, the existence of isoforms, species pharmacological differences and the high constitutive activity of the receptor were established. All these molecular findings have to be taken into account for the optimization of the ligands aiming at a clinical use. They show the interest of antagonists/inverse agonists in the symptomatic treatment of schizophrenia and cognitive and attentional deficits.
I didn't post that to quibble. When I look at histaminic neurotransmission as a system, I find major contradictions and conditional activities. Check out this abstract (and the final sentence, in particular):J Pharmacol Exp Ther. 2001 Dec;299(3):908-14.
Constitutive activity of histamine h(3) receptors stably expressed in SK-N-MC cells: display of agonism and inverse agonism by H(3) antagonists.Wieland K, Bongers G, Yamamoto Y, Hashimoto T, Yamatodani A, Menge WM, Timmerman H, Lovenberg TW, Leurs R.
Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Vrije Universiteit, Division of Chemistry, Amsterdam, The Netherlands.
Agonist-independent activity of G-protein-coupled receptor, also referred to as constitutive activity, is a well-documented phenomenon and has been reported recently for both the histamine H(1) and H(2) receptors. Using SK-N-MC cell lines stably expressing the human and rat H(3) receptors at physiological receptor densities (500-600 fmol/mg of protein), we show that both the rat and human H(3) receptors show a high degree of constitutive activity. The forskolin-mediated cAMP production in SK-N-MC cells is inhibited strongly upon expression of the G(i)-coupled H(3) receptor. The cAMP production can be further inhibited upon agonist stimulation of the H(3) receptor and can be enhanced by a variety of H(3) antagonists acting as inverse agonists at the H(3) receptor. Thioperamide, clobenpropit, and iodophenpropit raise the cAMP levels in SK-N-MC cells with potencies that match their receptor binding affinities. Surprisingly, impentamine and burimamide act as effective H(3) agonists. Modification of the amine group of impentamine dramatically affected the pharmacological activity of the ligand. Receptor affinity was reduced slightly for most impentamine analogs, but the functional activity of the ligands varied from agonist to neutral antagonist and inverse agonist, indicating that subtle changes in the chemical structures of impentamine analogs have major impact on the (de)activation steps of the H(3) receptor. In conclusion, upon stable expression of the rat and human H(3) receptor in SK-N-MC cells constitutive receptor activity is detected. In this experimental system, H(3) receptors ligands, previously identified as H(3) antagonists, cover the whole spectrum of pharmacological activities, ranging from full inverse agonists to agonists.
So, I have recently decided to steer clear of mechanisms. They seem to be post hoc rationalizations, and may be nothing more than the scientific equivalent to "The blind men and the elephant". All mechanistic explanations are inherently simplistic, IMHO, despite the complexity that is so obvious to us.Lar
Posted by DSCH on August 12, 2003, at 18:11:17
In reply to Re: H1 antagonists vs H3 antagonists » DSCH, posted by Larry Hoover on August 12, 2003, at 8:28:40
It looks as though there may be at least two subtypes of H3. Too lazy to post the relavant abstracts right now. ;) Had too much sugar for breakfast and it's been beating on me the whole day.
Posted by zenclearer on August 12, 2003, at 18:28:29
In reply to Re: Dexedrine, amino acids, and the heart » Zenclearer, posted by DSCH on August 11, 2003, at 20:09:41
I rather think the aminos might always cause me that problem; and I do take the other vitamins.
Strattera? Been there, done that. No thanks. :)
I think as natural as possible, with added basics is direction that may suit me best. Easier said than done!
This is the end of the thread.
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