Psycho-Babble Medication Thread 339744

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Re: Sounds like a question for CHEMIST! chemist

Posted by BarbaraCat on July 12, 2004, at 19:42:15

In reply to Re: Sounds like a question for CHEMIST! BarbaraCat, posted by chemist on July 12, 2004, at 17:39:35

Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat


> differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
>
>
> > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> >
> > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> >
> > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> >
> >
> > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > >
> > >
> > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > >
> > > > >
> > > >
> > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > >
> > > > Cheers,
> > > > Panda.
> > > >
> > >
> >
> >
>

 

Re: Sounds like a question for CHEMIST! BarbaraCat

Posted by chemist on July 12, 2004, at 19:53:57

In reply to Re: Sounds like a question for CHEMIST! chemist, posted by BarbaraCat on July 12, 2004, at 19:42:15

> Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat

no, thank you (and the other posters), it's interesting and rewarding to delve into new areas (i speak of myself)...please do keep us informed about the methylation business...let me throw another bone your way: when doubly-protonated, the side chain carries a formal charge. from my work with alkaloids that bind to ligand-gated ion channels of a certain flavor, i know that the binding affinity is greatly increased if one protonates the compound in question. i wonder if a similar antagonism is instigated if the epsilon nitrogen is protonated, and thus competitive binding to H_{1} become more non-competitive? food for thought.........let us know what you discover.......and since you asked, it is chemist, Ph.D. (that and $2.00 gets me a cup of coffee.......).....all the best, chemist
>
>
> > differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
> >
> >
> > > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> > >
> > > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> > >
> > > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> > >
> > >
> > > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > > >
> > > >
> > > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > > >
> > > > > >
> > > > >
> > > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > > >
> > > > > Cheers,
> > > > > Panda.
> > > > >
> > > >
> > >
> > >
> >
>
>

 

Re: Ooops, Seroquel doesn't block M1 chemist

Posted by Sad Panda on July 13, 2004, at 3:53:34

In reply to Re: Ooops, Seroquel doesn't block M1 Sad Panda, posted by chemist on July 12, 2004, at 15:00:55

> > > > Got a burning question for you Panda. After my recent bad experience with Seroquel, I have to agree with you. AP's are a bit overkill if all one wants is to get some sleep, and who knows what else is brewing in the chemical soup. I'm very curious as to my extreme and immediate reaction. Very difficult waking up, much like when I was taking trazodone. I felt quite depressed and out of it the 4 days I was on 6.25 or 12.5 pm. Very lethargic but jittery at the same time.
> > > >
> > > > My first thought was 'oh, I'm having a bad reaction to a reduction of dopamine - I need that dopamine'. Now, I realize that AP's reduce dopamine as part of their antipsychotic action, but I was under the impression Seroquel was not a heavy dopamine hitter. Also, none of these meds change neurotransmitter/receptor functionality that quickly, so dopamine doesn't seem a likely candidate. So perhaps the path is a similar 5Ht2-a blockade as w/trazodone and remeron, but we're still talking serotonin receptors and there's a lag time. It doesn't happen that quickly. My question is, is there also a histamine release which could account for the groggyness? Might this tie in with a possible dysfunction in my histamine levels? I haven't been tested for any of this but have been following the histadine/methylation theories. I'm also taking lithium and St. John's Wort (which is working surprisingly well). What could be at the root of the severe depression and restlessness I experienced immediately from Seroquel? After not taking it last night, I woke this morning fresh as a daisy and feeling sooooo much better. - Barbara
> > > >
> > > >
> > >
> > > Seroquel block Alpha-1 NE receptors the most, so I would possibly blame that. Coming in a close second is it's H1 blockade. At low doses I would say that's all it does as the next receptor is blocks is actually M1, so you'd probably notice a little dry mouth & constipation before 5-HT2A & D2 blockade ever comes to the party.
> > >
> > > On this page is a pretty good table showing the differences: http://www.vh.org/adult/provider/psychiatry/CPS/04.html#table2
> > >
> > > Cheers,
> > > Panda.
> > >
> >
> > Ooops, Ignore what I said about Seroquel probably causing antimuscarinic dry mouth & constipation. Most other websites say it doesn't block M1.
> >
> > Cheers,
> > Panda.
> >
> >
> >
> panda, i'm not letting you off the hook so easily, having recently pronounced you the expert. my PDR white-sheet from astrazeneca says ``no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors (IC_{50s} > 5000 nM).'' given an IC_{50} for D_{1} at 1268 nM and IC_{50} of 329 nM for D_{2}, what's an order of magnitude or two among friends? you're still in charge...... :) all the best, chemist
>
>

Hi Chemist,

Looks like I am half-wrong or half-right, Seroquel's monograph says it has no affinity for muscarinic receptors, yet constipation is high on the list of side effects straight after dry mouth. I know Alpha-1 blockade produces dry mouth, but what causes constipation beside M1 blockade?

Cheers,
Panda.


 

Re: Ooops, Seroquel doesn't block M1 Sad Panda

Posted by chemist on July 13, 2004, at 8:22:48

In reply to Re: Ooops, Seroquel doesn't block M1 chemist, posted by Sad Panda on July 13, 2004, at 3:53:34

> > > > > Got a burning question for you Panda. After my recent bad experience with Seroquel, I have to agree with you. AP's are a bit overkill if all one wants is to get some sleep, and who knows what else is brewing in the chemical soup. I'm very curious as to my extreme and immediate reaction. Very difficult waking up, much like when I was taking trazodone. I felt quite depressed and out of it the 4 days I was on 6.25 or 12.5 pm. Very lethargic but jittery at the same time.
> > > > >
> > > > > My first thought was 'oh, I'm having a bad reaction to a reduction of dopamine - I need that dopamine'. Now, I realize that AP's reduce dopamine as part of their antipsychotic action, but I was under the impression Seroquel was not a heavy dopamine hitter. Also, none of these meds change neurotransmitter/receptor functionality that quickly, so dopamine doesn't seem a likely candidate. So perhaps the path is a similar 5Ht2-a blockade as w/trazodone and remeron, but we're still talking serotonin receptors and there's a lag time. It doesn't happen that quickly. My question is, is there also a histamine release which could account for the groggyness? Might this tie in with a possible dysfunction in my histamine levels? I haven't been tested for any of this but have been following the histadine/methylation theories. I'm also taking lithium and St. John's Wort (which is working surprisingly well). What could be at the root of the severe depression and restlessness I experienced immediately from Seroquel? After not taking it last night, I woke this morning fresh as a daisy and feeling sooooo much better. - Barbara
> > > > >
> > > > >
> > > >
> > > > Seroquel block Alpha-1 NE receptors the most, so I would possibly blame that. Coming in a close second is it's H1 blockade. At low doses I would say that's all it does as the next receptor is blocks is actually M1, so you'd probably notice a little dry mouth & constipation before 5-HT2A & D2 blockade ever comes to the party.
> > > >
> > > > On this page is a pretty good table showing the differences: http://www.vh.org/adult/provider/psychiatry/CPS/04.html#table2
> > > >
> > > > Cheers,
> > > > Panda.
> > > >
> > >
> > > Ooops, Ignore what I said about Seroquel probably causing antimuscarinic dry mouth & constipation. Most other websites say it doesn't block M1.
> > >
> > > Cheers,
> > > Panda.
> > >
> > >
> > >
> > panda, i'm not letting you off the hook so easily, having recently pronounced you the expert. my PDR white-sheet from astrazeneca says ``no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors (IC_{50s} > 5000 nM).'' given an IC_{50} for D_{1} at 1268 nM and IC_{50} of 329 nM for D_{2}, what's an order of magnitude or two among friends? you're still in charge...... :) all the best, chemist
> >
> >
>
> Hi Chemist,
>
> Looks like I am half-wrong or half-right, Seroquel's monograph says it has no affinity for muscarinic receptors, yet constipation is high on the list of side effects straight after dry mouth. I know Alpha-1 blockade produces dry mouth, but what causes constipation beside M1 blockade?
>
> Cheers,
> Panda.
>
>
>
hey panda the only thing i can think of would implicate smooth muscle. this would involve adenosine (and the ATP cycle) in some way, although i can't seem to get from ``here to there.'' i think we need to call larry hoover in on this one......all the best, chemist

 

Re: okay, here we go... (new cocktail) chemist

Posted by cpallen79 on July 13, 2004, at 12:13:49

In reply to Re: okay, here we go... cpallen79, posted by chemist on July 12, 2004, at 17:46:33

Hey Chemist,
I went to my PDOC today! here's the new "cocktail" we are going to try.

Luvox- probably get upt to around 200 MGS
Trazedone- around 25 mgs
Adderall XR- 5 mgs
Ativan as needed

I am reluctant to take ativan, but my PDOC is very concerned about my anxiety and agitation of course, both of have been major cornerstones of my depression. We've also discussed the posssiblity of using an anticonvulsant/mood stabilizer to help with anxiety and agitation. Lamitcal came up, I told her I'd consider it.... just gotta watch out for that pesky rash of course! :)

 

Re: okay, here we go... (new cocktail) cpallen79

Posted by BarbaraCat on July 13, 2004, at 13:57:09

In reply to Re: okay, here we go... (new cocktail) chemist, posted by cpallen79 on July 13, 2004, at 12:13:49

I have my own very strong feelings on Lamictal, having come down with Stevens Johnson Syndrome rash and worse. Was sick, sick, sick for 5 weeks. It was not directly due to Lam, although I'm sure it predisposed and sensitized me to sulfa meds (where I'd never had a problem before) because I was getting weird little itches and skin sensitivities the whole time I was taking it, but ignoring those signs as I was looking for 'rash'. Lamictal is not an antianxiety by a long shot. It was activating at each new dose, although it did help with depression. But it did nothing for my agitation except to perhaps reframe the feeling into a 'buzz'.

I have had good luck on Gabapentin, although others may disagree. It's short acting and works on GABA receptors in a different manner than benzos. As long as I don't take it all the time I can get a very nice gentle relaxer from it at around 900mg.

Another thing worth trying is the amino acid L-Taurine. it's had good press as a mood stabilizer and I've found it to be very relaxing and helpful with bipolar symptoms. I take 2M twice a day (if you opt to try Gabapentin, don't take it at the same time since they compete). IMHO, anyone who is taking an antidepressant should consider taking a mood stabiliser. Potentiates their action and smooths the effect. I happen to LOVE lithium, but I'm probably in the minority. And don't hesitate to take a benzo when you really need one. The shorter half-lifers like Serax and ativan shouldnt' product any addiction problems. They won't leave you a smiling blissed out yogi, that's for certain, but they will take the edge off without worrying about developing a jones from them. Ativan is a very good benzo and will allow you to function so treat it like a security blanket. It's there if you need it and that's sometimes enough to take the edge off. - Barbara

> Hey Chemist,
> I went to my PDOC today! here's the new "cocktail" we are going to try.
>
> Luvox- probably get upt to around 200 MGS
> Trazedone- around 25 mgs
> Adderall XR- 5 mgs
> Ativan as needed
>
> I am reluctant to take ativan, but my PDOC is very concerned about my anxiety and agitation of course, both of have been major cornerstones of my depression. We've also discussed the posssiblity of using an anticonvulsant/mood stabilizer to help with anxiety and agitation. Lamitcal came up, I told her I'd consider it.... just gotta watch out for that pesky rash of course! :)

 

Re: Sounds like a question for CHEMIST! chemist

Posted by BarbaraCat on July 13, 2004, at 14:41:36

In reply to Re: Sounds like a question for CHEMIST! BarbaraCat, posted by chemist on July 12, 2004, at 19:53:57

I realized after posting this that I made a serious gender blunder. You may be a Ph.D. (which you are), but here I am assuming you're a Mr., whereas nothing in your posts gives me reason to believe you are not a Ms!. No biggie, just amusing to catch myself hoisted on my own 'liberated' petard.

Thanks for your thorough replies to my and all of our questions. You are truly a blessing on this board and always so responsive. I speak for us all when I say we've learned much from you and you're a great asset.

I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning. The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.

The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.

So I will be busy with all my books and papers following the tail of methyl doners, histamines and into all the caverns and crannies this will lead me to. Any pointers would be appreciated. But mercy! I have some organic chemistry and neurobiology under my belt, but am by no means 'Mrs. Science'. Take care and thanks. - Barbara


> > Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat
>
> no, thank you (and the other posters), it's interesting and rewarding to delve into new areas (i speak of myself)...please do keep us informed about the methylation business...let me throw another bone your way: when doubly-protonated, the side chain carries a formal charge. from my work with alkaloids that bind to ligand-gated ion channels of a certain flavor, i know that the binding affinity is greatly increased if one protonates the compound in question. i wonder if a similar antagonism is instigated if the epsilon nitrogen is protonated, and thus competitive binding to H_{1} become more non-competitive? food for thought.........let us know what you discover.......and since you asked, it is chemist, Ph.D. (that and $2.00 gets me a cup of coffee.......).....all the best, chemist
> >
> >
> > > differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
> > >
> > >
> > > > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> > > >
> > > > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> > > >
> > > > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> > > >
> > > >
> > > > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > > > >
> > > > >
> > > > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > > > >
> > > > > > >
> > > > > >
> > > > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > > > >
> > > > > > Cheers,
> > > > > > Panda.
> > > > > >
> > > > >
> > > >
> > > >
> > >
> >
> >
>

 

Re: okay, here we go... (new cocktail) cpallen79

Posted by chemist on July 13, 2004, at 15:02:31

In reply to Re: okay, here we go... (new cocktail) chemist, posted by cpallen79 on July 13, 2004, at 12:13:49

> Hey Chemist,
> I went to my PDOC today! here's the new "cocktail" we are going to try.
>
> Luvox- probably get upt to around 200 MGS
> Trazedone- around 25 mgs
> Adderall XR- 5 mgs
> Ativan as needed
>
> I am reluctant to take ativan, but my PDOC is very concerned about my anxiety and agitation of course, both of have been major cornerstones of my depression. We've also discussed the posssiblity of using an anticonvulsant/mood stabilizer to help with anxiety and agitation. Lamitcal came up, I told her I'd consider it.... just gotta watch out for that pesky rash of course! :)


hello there, chemist here....the cocktail you describe looks promising. friend, do not fear the ativan: if you feel uncomfortable, use it. that's what it's there for. please keep us informed of how things are going, and i wish you all the best, chemist

 

i got Panda-ed!!! BarbaraCat

Posted by chemist on July 13, 2004, at 16:30:11

In reply to Re: Sounds like a question for CHEMIST! chemist, posted by BarbaraCat on July 13, 2004, at 14:41:36

hello there, you'll notice the title of this post. not too long ago, i referred to sad panda as ``he'' in a post, and another poster asked why i assumed that sad panda was a male. i replied that i didn't know, and i recall that panda was simply tickled by the whole question of he/she. as am i, honored to join San Panda as the subject of a gender inquiry. on another note, you sound like you know your stuff: are you a chemist, biologist, m.d., if you don't mind my asking? and please keep us informed on your digging into the histamine/histidine business, it is quite intriguing......all the best, cHEmist

> I realized after posting this that I made a serious gender blunder. You may be a Ph.D. (which you are), but here I am assuming you're a Mr., whereas nothing in your posts gives me reason to believe you are not a Ms!. No biggie, just amusing to catch myself hoisted on my own 'liberated' petard.
>
> Thanks for your thorough replies to my and all of our questions. You are truly a blessing on this board and always so responsive. I speak for us all when I say we've learned much from you and you're a great asset.
>
> I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning. The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.
>
> The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.
>
> So I will be busy with all my books and papers following the tail of methyl doners, histamines and into all the caverns and crannies this will lead me to. Any pointers would be appreciated. But mercy! I have some organic chemistry and neurobiology under my belt, but am by no means 'Mrs. Science'. Take care and thanks. - Barbara
>
>
> > > Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat
> >
> > no, thank you (and the other posters), it's interesting and rewarding to delve into new areas (i speak of myself)...please do keep us informed about the methylation business...let me throw another bone your way: when doubly-protonated, the side chain carries a formal charge. from my work with alkaloids that bind to ligand-gated ion channels of a certain flavor, i know that the binding affinity is greatly increased if one protonates the compound in question. i wonder if a similar antagonism is instigated if the epsilon nitrogen is protonated, and thus competitive binding to H_{1} become more non-competitive? food for thought.........let us know what you discover.......and since you asked, it is chemist, Ph.D. (that and $2.00 gets me a cup of coffee.......).....all the best, chemist
> > >
> > >
> > > > differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
> > > >
> > > >
> > > > > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> > > > >
> > > > > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> > > > >
> > > > > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> > > > >
> > > > >
> > > > > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > > > > >
> > > > > >
> > > > > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > > > > >
> > > > > > > >
> > > > > > >
> > > > > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > > > > >
> > > > > > > Cheers,
> > > > > > > Panda.
> > > > > > >
> > > > > >
> > > > >
> > > > >
> > > >
> > >
> > >
> >
>
>

 

Re: i got Panda-ed!!! - TOO FUNNY! (nm)

Posted by KaraS on July 13, 2004, at 17:43:30

In reply to i got Panda-ed!!! BarbaraCat, posted by chemist on July 13, 2004, at 16:30:11

 

Re: BarbarCat, i got Panda-ed!!!

Posted by KaraS on July 13, 2004, at 20:10:21

In reply to i got Panda-ed!!! BarbaraCat, posted by chemist on July 13, 2004, at 16:30:11

BarbaraCat, I am the one who initially "Panda-ed" Chemist by bringing up the same issue that you did. Like you, I found myself making assumptions about the gender of various posters without justification. I love the way you described it: "hoisted on my own 'liberated' petard". That's perfect!

At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).

KaraS

 

Re: BarbarCat, i got Panda-ed!!! KaraS

Posted by BarbaraCat on July 14, 2004, at 11:44:09

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 13, 2004, at 20:10:21


> At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
>
**Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.


 

Re: BarbarCat, i got Panda-ed!!! BarbaraCat

Posted by cpallen79 on July 14, 2004, at 12:46:26

In reply to Re: BarbarCat, i got Panda-ed!!! KaraS, posted by BarbaraCat on July 14, 2004, at 11:44:09

> Ditto! I hope he comes back!!! I can't imagine not having chemist around!


> > At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
> >
> **Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.
>
>
>

 

Re: BarbarCat, i got Panda-ed!!!

Posted by KaraS on July 14, 2004, at 15:46:06

In reply to Re: BarbarCat, i got Panda-ed!!! KaraS, posted by BarbaraCat on July 14, 2004, at 11:44:09

>
> > At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
> >
> **Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.
>
>
>

A week really isn't that long and I'm sure he'll be back as soon as he can (knowing him) and will pick up where he left off.

 

Re: BarbarCat, i got Panda-ed!!! KaraS

Posted by karen_kay on July 14, 2004, at 22:19:12

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 14, 2004, at 15:46:06

hey all! i've been dumpster diving (archiving as you commoners call it) and i found chemist's email addy (in case anyone wants to keep in touch). i email him and he always returns his emails (sometimes he blows kisses too, but only if you're very very nice :)

it's todd at lanczos dot cm dot utexas dot edu


the link for his email addy is

http://www.dr-bob.org/babble/20040712/msgs/365398.html

(ha, did you think i was lying? not this time :)

he hangs out in open sometimes (but only if you're very, very lucky (wait, is it very, very unlucky? your choice i suppose..))

tootles..... i'm sure he'd like some company while he's in solitary confinement...

kk

oh, and you've been kk-ed, i'm a she!!! (though i noticed there's another kk floating around here somewhere.. i'll have to catch up with that person... this could get very interesting folks.. keep your eyes open!

 

Re: BarbarCat, i got Panda-ed!!!

Posted by KaraS on July 15, 2004, at 1:44:12

In reply to Re: BarbarCat, i got Panda-ed!!! KaraS, posted by karen_kay on July 14, 2004, at 22:19:12

You are too funny, kk (the real/original kk)!! Thanks for Chemist's address. I'll have to drop him a line. He knew his exile was coming but he fought the good fight anyway. I also hope he can survive his solitary confinement for the week.

I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)

Take care,
Kara

 

Re: BarbarCat, i got Panda-ed!!!

Posted by BarbaraCat on July 15, 2004, at 9:41:36

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 15, 2004, at 1:44:12

Texas! That's a kick! Can't you just imagine Chemist with a Texan Twang? That is too precious. I thought he was Aussie. Hey Chemist, you're missed! - BCat

>> I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)
>
> Take care,
> Kara

 

Re: BarbarCat, i got Panda-ed!!! BarbaraCat

Posted by Racer on July 15, 2004, at 12:27:46

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by BarbaraCat on July 15, 2004, at 9:41:36

Hey, BararaCat - chemist asked me to post his email to you, since he can't respond here. Taken from a thread below:
todd at lanczos dot cm dot utexas dot edu
(I'm guessing the "dot cm" is actually "dot com")

He is missed. He really is an asset to our community here. Still, it's only a week...

 

Re: BarbarCat, i got Panda-ed!!! Racer

Posted by cpallen79 on July 15, 2004, at 12:30:58

In reply to Re: BarbarCat, i got Panda-ed!!! BarbaraCat, posted by Racer on July 15, 2004, at 12:27:46

I miss Chemist too, he really is an asset to us, tell him I say hi!

 

Re: BarbarCat, sorry -- it is cm (nm)

Posted by Racer on July 15, 2004, at 14:58:51

In reply to Re: BarbarCat, i got Panda-ed!!! BarbaraCat, posted by Racer on July 15, 2004, at 12:27:46

 

Re: BarbarCat, i got Panda-ed!!!

Posted by KaraS on July 15, 2004, at 16:32:39

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by BarbaraCat on July 15, 2004, at 9:41:36

> Texas! That's a kick! Can't you just imagine Chemist with a Texan Twang? That is too precious. I thought he was Aussie. Hey Chemist, you're missed! - BCat
>


I can't imagine him with a Texan twang at all either. Maybe he just moved there from somewhere else (like Britain or Australia) for work purposes. I need to keep reading his posts with a British accent so I think I 'll stick with that theory!

Yes, you are missed Chemist!!!

-K

> >> I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)
> >
> > Take care,
> > Kara
>
>

 

Re: BarbarCat, i got Chem-ed!!!

Posted by Sad Panda on July 15, 2004, at 17:44:29

In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 15, 2004, at 16:32:39

Chemist is sorely missed, he always seems to have the facts. :(

If it helps, imagine that Chemist sounds like George W. :D

Cheers,
Panda.

 

Re: BarbarCat, i got Chem-ed!!!

Posted by KaraS on July 15, 2004, at 19:05:37

In reply to Re: BarbarCat, i got Chem-ed!!!, posted by Sad Panda on July 15, 2004, at 17:44:29

> Chemist is sorely missed, he always seems to have the facts. :(
>
> If it helps, imagine that Chemist sounds like George W. :D
>
> Cheers,
> Panda.
>

He's the last person in the world I'd like to think that Chemist sounds like!!!

- Kara

 

Re: let's stay focused on medication here, thanks (nm)

Posted by Dr. Bob on July 15, 2004, at 19:27:38

In reply to Re: BarbarCat, i got Chem-ed!!!, posted by KaraS on July 15, 2004, at 19:05:37

 

Re: Sounds like a question for CHEMIST! BarbaraCat

Posted by Larry Hoover on July 18, 2004, at 11:23:45

In reply to Re: Sounds like a question for CHEMIST! chemist, posted by BarbaraCat on July 13, 2004, at 14:41:36

> I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning.

Easy enough to supplement to target methyl donation.....betaine and B-12.

> The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.

DMPS has a substantial impact on all metal cations. If I recall correctly, it is about 30 times more effective at removing zinc than mercury. Serious business, using chelation therapy. All too often, it is poorly managed, from a medical perspective. If mercury is a potential toxicant, take selenium. It will covalently bond to the mercury, totally inactivating it. The solubility constant for Se-Hg is on the order of ten to the -70. In other words, you would require roughly 10 to 46th power litres of water to dissolve one molecule. In other other words, it is so insoluble that its solubility can't be measured. The mercury will stay in your body, but it will be totally inert.

Thiol/sulphur metabolism is absolutely disturbed in fibromyalgia. That's why I've been pushing taurine. It's the sulphonic acid version of GABA.

> The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.

Niacinamide down-regulates histamine synthesis, and also blocks mast-cell degranulation (histamine release). It also, coincidentally, is an agonist at GABA receptors.

FASEB J. 2003 Aug;17(11):1377-9.

Nicotinamide: a potential addition to the anti-psoriatic weaponry.

Namazi MR.

Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran. namazi_mr@yahoo.com

Psoriasis is an inflammatory disorder characterized by a T helper type 1 cell cytokine pattern. Increased expression of adhesion molecules, prominent neutrophil accumulation, and increased production of nitric oxide are characteristics of this disorder. Moreover, histamine and proteases are supposed to participate in the pathogenesis of psoriasis. Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-alpha production, nicotinamide produces a mild TH2 bias. Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis and mast cell histamine release. It inhibits nitric oxide synthase mRNA induction and suppresses antigen-induced lymphocyte transformation. Nicotinamide increases the biosynthesis of ceramides, which upon degradation produce sphingosine. Sphingosine inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC. Taken together, it can be reasoned that nicotinamide could be a useful addition to anti-psoriatic armamentarium. The combination of nicotinamide and thalidomide or methotrexate provided a powerful synergistic inhibition of murine collagen-induced arthritis. Nicotinamide decreased the methotrexate-induced hepatotoxicity. The above combinations may prove to have a powerful anti-psoriatic effect as well. As PARP inhibitors could exert anti-retroviral effect, nicotinamide could also be of special value in the treatment of HIV-infected psoriatics.

I expect this topic to be redirected, but I hope that a greater audience is exposed to some of these concepts, here on the main Babble board. Alternative medicine is drug-augmentative. There's a lot more you can do than get prescriptions filled.

Lar


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