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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by Sigolène on July 17, 2002, at 2:06:10
There is something i don't understand. Maybe semeone can explain me.
When they prescribe an antipsychotic (risperdal) together with an AD, they have the opposite effect. One is increasing 5 HT, the other is decreasing it !
The same when you have antipsychotic with ritalin, on is increasing dopamine, the other is decreasing it.
How can these meds be prescribed together ?
Posted by cybercafe on July 17, 2002, at 2:44:16
In reply to enhancing and decreasing the same neurotransmitter, posted by Sigolène on July 17, 2002, at 2:06:10
> There is something i don't understand. Maybe semeone can explain me.
> When they prescribe an antipsychotic (risperdal) together with an AD, they have the opposite effect. One is increasing 5 HT, the other is decreasing it !
> The same when you have antipsychotic with ritalin, on is increasing dopamine, the other is decreasing it.
> How can these meds be prescribed together ?
antipsychotics don't decrease a neurotransmitter, they block a specific receptor...in other words ... you would be right if an antipsychotic blocked all of the D1, D2, D3,D4 and D5 dopamine receptors and you also took a drug that increased synaptic dopamine level.. however i believe the antipsychotics you are referring to only block one of the dopamine receptors -- D2 -- and only a few of the serotonin receptors 5HT2A and others ... ?
... another interesting effect is that if you take an antipsychotic and block a receptor, that leaves more dopamine available for the other receptors ... so the antipsychotic effectively increases the dopamine content in the synapse ...
Posted by Sigolène on July 17, 2002, at 5:00:26
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by cybercafe on July 17, 2002, at 2:44:16
Tank you for your explaination.
I know that antipsychotics are blocking receptors and not decreasing anything directly. But i mean, if we block a specific receptor, then we decrease the effect of the neurotransmitter. So, in one way we stimulate (by blocking 5HT reuptake for example) and on the other way we decrease the effect of 5HT or DA, even if it doesn't concern all the 5HT or DA receptors. Do you still think it's logical ?
Posted by hawkeye on July 18, 2002, at 6:04:03
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by cybercafe on July 17, 2002, at 2:44:16
RE:-->> "... another interesting effect is that if you take an antipsychotic and block a receptor, that leaves more dopamine available for the other receptors ... so the antipsychotic effectively increases the dopamine content in the synaps." <<--
-------------------------------------------------
I remembered reading this excerpt from the book "Blaming ther Brain" and thought I'd pass it along. The book was published approx. 4 years ago and is authored by a Professor of Psychiatry at a major UK Medical School. In matters of the human psyche, nothing is simple."Another major problem for the theory that schizophrenia is caused by excessive dopamine activity is that antipsychotic drugs, as is also true of the antidepressants, generally take several weeks before they exhibit any significant therapeutic effect. This is true despite the fact that it has been demonstrated that the drugs block dopamine receptors in a matter of hours. After several weeks of drug treatment, there is a compensatory increase in the number of dopamine receptors and an increase in the firing rate of dopamine neurons. The increase in the number of receptors should increase the capacity of neurons to respond to dopamine, and when combined with an increase in firing rate of dopamine neurons and a consequent increase in the amount of dopamine released, dopamine activity might be expected to increase rather than decrease at the time that antipsychotic drugs first seem to be working-hardly a change that shouid correct excessive dopamine activity.
There have been some attempts to resolve this paradox by resorting to explanations based on what is known about the anatomical distribution of many D2 receptors. Many of the D2 receptors, which have been hypothesized to be critically involved in schizophrenia, are "autoreceptors." An "autoreceptor," which is located on the body of dopamine reieasing neurons, acts like a brake, slowing the firing rate of dopamine neurons and decreasing the amount of dopamine released. If these autoreceptors are blocked by a drug, it has the effect of removing a brake (or stepping on the gas pedal), and the neuron's firing rate is increased. As most antipsychotic drugs block D2 autoreceptors, this should produce an increase in the firing rate of dopamine neurons and an increase in the amount of dopamine released into synapses. Once again, a paradox appears, as an increase in the firing rate of dopamine neurons would seem to be just the opposite ofwhat a drug shouid do in order to alleviate a theorized dopamine hyperactivity.
In an attempt to resolve the paradox, it has been suggested that when neurons fire at an abnormaiiy high rate for about a three-week period, their celi membranes "depolarize." Depolarization refers to a reduction in the voìtage differential between the celi membrane and the cytopiasm within the neuron, a condition that biocks the ability of a neuron to fire and to release its transmitter. It has been reported in a recent study that the capacity of chronic administration of different antipsychotic drugs to produce depolarization block of dopamine neurons was reiated to their antipsychotic efflcacy in humans." depolarization effects of antipsychotic drugs believe that there is no reason to think that depolarization represents a return to the normal state of the dopamine system, and they conclude that there is probably nothing at all wrong with the dopamine system in schizophrenics."
http://digilander.libero.it/nopazzia/Valenstein/davalenstein.htm
Posted by hawkeye on July 18, 2002, at 6:29:37
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by hawkeye on July 18, 2002, at 6:04:03
Last paragraph in quote in above post dhpould read:
"In an attempt to resolve the paradox, it has been suggested that when neurons fire at an abnormaiiy high rate for about a three-week period, their celi membranes "depolarize." Depolarization refers to a reduction in the voìtage differential between the celi membrane and the cytopiasm within the neuron, a condition that biocks the ability of a neuron to fire and to release its transmitter. It has been reported in a recent study that the capacity of chronic administration of different antipsychotic drugs to produce depolarization block of dopamine neurons was reiated to their antipsychotic efflcacy in humans. While the depolarization block phenomenon may prove useful for screening new antipsychotic drugs, its significance for the dopamine theory of schizophrenia is not at all clear. The principal researchers working on the depolarization effects of antipsychotic drugs believe that there is no reason to think that depolarization represents a return to the normal state of the dopamine system, and they conclude that there is probably nothing at all wrong with the dopamine system in schizophrenics."
Posted by cybercafe on July 18, 2002, at 13:14:52
In reply to Correction Last Post, posted by hawkeye on July 18, 2002, at 6:29:37
>and the cytopiasm within the neuron, a condition that biocks the ability of a neuron to fire and to release its transmitter. It has been reported
actually i think depolarization occurs when sodium or calium or other positively charged ions diffuse across a potential different (polarization) and therefore reduce the polarization (depolarization)... this causes neurons to fire! ... however what makes things a bit more complicated is that as the neurons fire i believe sodium channels close to limit just how depolarized the cell gets... and then instead of getting rid of these positive Na ions, we pump out potassium K ions... since Na ions are in a greater concentration outside the cell they would have to be actively PUMPED out.. whereas since K ions are at a greater concentration INSIDE the cell, we can just let them DIFFUSE out... (much faster)....
basically sodium channels close after a certain amount of sodium enters the cell, so that too much sodium doesn't enter the cell (because the concentration inside the cell is always carefully maintained at about one tenth of the concentration outside the cell).... and for the neuron to fire again, these channels have to open again! ... also you have to wait for the time it takes for the potassium to be pumped out of the cell ....so basically when a cell fires, it lots of positive ions on the inside and becomes positive, in order for it to fire again it has to become negative again, and so you have to pump out the ions that made it positive.. this takes time.... depending on how long this takes, and how you alter the time it takes, by causing a cell to fire you are making it harder for it to fire again.... so in a way the firing of XXX neurons causes a decrease in the firing of XXX neurons
>believe that there is no reason to think that depolarization represents a return to the normal state of the dopamine system, and they conclude that there is probably nothing at all wrong with the dopamine system in schizophrenics."
wait a sec here ....
depolarization = not a normal dopamine system
schizophrenic treatment = provide for not a normal dopamine system (change their dopamine system)
changing schizophrenic dopamine system = therapeutic effectsso if changing the system results in therapeutic effects....
if
old system = problems
new system = problems solvedthen why would you say that there is nothing wrong with the dopamine system in schizophrenics?
Posted by Shawn. T. on July 18, 2002, at 20:10:48
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by hawkeye on July 18, 2002, at 6:04:03
Schizophrenia is a serotonergic problem, not a dopaminergic problem. A drug need not have any effects on dopamine receptors to be an effective schizophrenia treatment. Serotonin 5-HT2a and
5-HT2c receptors are one of the body's most important regulatory mechanisms. They control cortisol excretion, dopamine levels, etc. Indirectly, these two receptors have a huge impact on the body. Excessive dopamine activity is a problem in schizophrenia, but giving people with this disorder drugs that effect dopamine receptors is an ill conceived notion. I've already provided so many links to support what I'm saying, so I'm just going to let my words stand. For some nice suggestions on dietary supplements to reduce symptoms of schizophrenia, go to the following link and scroll down to schizophrenia. M,100,907 plus this knowledge will help to defeat schizophrenia.
http://www.gnc.com/health_notes/concerns.asp"In the United States, 25% of all hospital beds are occupied by people with schizophrenia."
Shawn
Posted by katekite on July 22, 2002, at 11:00:12
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by Shawn. T. on July 18, 2002, at 20:10:48
I'm unclear on what you think. I've read most of your posts but find it hard to distinguish between plugs for particular drugs and what you think the actual mechanisms of disease and treatment should be, and what you think is a hypothesis and what you think is the bare truth.
So if you could answer a few questions it would help me to put together what you think. thanks. You bring up a lot of points which are interesting to think about.
Do you think treatment based at the 5HT2 receptor alone will control schizophrenic symptoms?
Do you think a drug with 5HT2 antagonism could more effectively treat schizophrenia than a drug that also blocks D2 receptors?
Do you think shizophrenics should ever be treated with the older-type anti-psychotics that do not affect 5HT2?
Do you think that schizophrenia is due to a problem with under-control by serotonin? OR is it due to a problem with dopamine/receptors. OR is it both?
Do you think that all schizophrenia is due to the same problem? Or is it like insomnia, a common final pathway from multiple possible original problems?
Thanks,
kate
Posted by Shawn. T. on July 22, 2002, at 15:19:25
In reply to Re: enhancing and decreasing » Shawn. T., posted by katekite on July 22, 2002, at 11:00:12
> I'm unclear on what you think. I've read most of your posts but find it hard to distinguish between plugs for particular drugs and what you think the actual mechanisms of disease and treatment should be, and what you think is a hypothesis and what you think is the bare truth.
>
My primary goal is to warn people that certain drugs are either ineffective or have unnecessary side effects. If I am going to warn people about what not to take, I have to provide them with some alternatives.> So if you could answer a few questions it would help me to put together what you think. thanks. You bring up a lot of points which are interesting to think about.
>
> Do you think treatment based at the 5HT2 receptor alone will control schizophrenic symptoms?
>
Yes, but I think adding on fish oils to that sort of treatment would be wise.> Do you think a drug with 5HT2 antagonism could more effectively treat schizophrenia than a drug that also blocks D2 receptors?
>
They should treat the symptoms equally well. Blocking D2 receptors causes side effects and is unnecessary.> Do you think shizophrenics should ever be treated with the older-type anti-psychotics that do not affect 5HT2?
>
Never.> Do you think that schizophrenia is due to a problem with under-control by serotonin? OR is it due to a problem with dopamine/receptors. OR is it both?
>
It has nothing to do with a problem with dopamine receptors. It has everything to do with a lack of certain serotonin receptors' ability to modulate dopamine levels (and possibly other things in the body as well).> Do you think that all schizophrenia is due to the same problem? Or is it like insomnia, a common final pathway from multiple possible original problems?
>
I believe it's due to the same problem, but everyone's brain and past environment is different
of course. This one I can't prove; I'm simply stating an opinion here.> Thanks,
> kateYou're welcome,
Shawn
Posted by katekite on July 22, 2002, at 17:12:50
In reply to Re: enhancing and decreasing » katekite, posted by Shawn. T. on July 22, 2002, at 15:19:25
Thanks Shawn. I think as time has gone by you've refined what you think and maybe I haven't been reading close enough, so I felt a bit confused.
I'm curious what you think about why people with Parkinson's often develop schizophrenia type illness when treated with L-dopa or other dopaminergic drugs? That's the one thing I just can't make that fit with the 5HT2 theory. Because their brains clearly have death of dopamine neurons. So it just seems like it would be a dopamine problem. Do you have any thoughts?
kate
Posted by cybercafe on July 22, 2002, at 21:16:21
In reply to Re: enhancing and decreasing » Shawn. T., posted by katekite on July 22, 2002, at 17:12:50
> I'm curious what you think about why people with Parkinson's often develop schizophrenia type illness when treated with L-dopa or other dopaminergic drugs? That's the one thing I just can't make that fit with the 5HT2 theory. Because their brains clearly have death of dopamine neurons. So it just seems like it would be a dopamine problem. Do you have any thoughts?
Yes it is very likely related to dopamine on some degree, I think schizophrenics might have more dopamine causing excessive firing of D2 receptors in the neocortex i don't remember exactly though
what i can tell you for certain that is i just got a report in the mail showing that the genes encoding norepinephrine (alpha1, 2, 3 beta1, 2), dopamine D2 and D4 corticosteroid and a particular G protein subunit are not shown to be altered in schizophrenia ...
in fact i believe schizophrenics seem to have enlarged ventricles (lateral cerebral ventricles) caused by death or a lack of growth of normal brain cells around the ventricles... i believe it is actually the hippocampus that is decreased in size in schizophrenics... i think failure of the hippocampus to filter out information from the cognitive brain centers (neocortex) to the emotional centers (limbic system) can cause overstimulation ....
Posted by Shawn. T. on July 23, 2002, at 19:11:16
In reply to Re: enhancing and decreasing, posted by cybercafe on July 22, 2002, at 21:16:21
Schizophrenia definitely involves dopamine neurons, but no drugs acting solely on dopamine receptors will effectively treat schizophrenia.
Drugs with effects on both dopamine and 5-HT2 receptors are better, but the side effects are undesirable.Parkinson's disease is a degeneration of dopaminergic cells in the substantia nigra. L-dopa is a precursor to dopamine, so when a person with Parkinson's disease is given this amino acid, dopamine levels are increased throughout the brain. This is not exactly ideal; all of the dopamine pathways in the brain will be affected by levodopa. Parkinson's disease primarily affects dopamine neurons projecting from the substantia nigra to the dorsal striatum and caudate putamen areas of the brain. This pathway is associated with the iniation of motor plans and motor coordination. Now the reason that l-dopa causes schizophrenia like side effects is because it also affects dopamine neurons in the ventral tegmental area that project to the ventral striatum (nucleus accumbens), amygdala, and prefrontal cortex. Hyperactivity of dopamine neurons in the pathway results in dystonia and psychosis. I'm curious about what effects M 100907 would have on Parkinson's disease.
This makes me angry (I just had to throw it in):
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=29834771On M-100907 (thromboembolism means the blocking of a blood vessel by a blood clot dislodged from its site of origin).
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=30302462More on that (plus some information on ketanserin, which is definitely not a highly selective 5-HT2 receptor antagonist):
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=29749349More on AT-1015 (anyone know who has the patent?)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=30820763I apologize for my former lack of knowledge. I am now a lot more up to date with the things that we have learned in the past two years. I have definitely realized that I am going to have to teach myself a lot of cell biology. You really can't make much headway with regards to understanding this stuff when you look solely at the brain in terms of its macro functions. I'm really convinced that bipolar disorders are related to 5-HT2 receptors, although I haven't done much research on that yet. This is because 5-HT2 receptors are excitatory and act through the phospholipase C/ inositol phosphate pathway (I don't believe that any other serotonin receptors directly affect this pathway). How about that.
Shawn
> > I'm curious what you think about why people with Parkinson's often develop schizophrenia type illness when treated with L-dopa or other dopaminergic drugs? That's the one thing I just can't make that fit with the 5HT2 theory. Because their brains clearly have death of dopamine neurons. So it just seems like it would be a dopamine problem. Do you have any thoughts?
>
> Yes it is very likely related to dopamine on some degree, I think schizophrenics might have more dopamine causing excessive firing of D2 receptors in the neocortex i don't remember exactly though
>
> what i can tell you for certain that is i just got a report in the mail showing that the genes encoding norepinephrine (alpha1, 2, 3 beta1, 2), dopamine D2 and D4 corticosteroid and a particular G protein subunit are not shown to be altered in schizophrenia ...
>
> in fact i believe schizophrenics seem to have enlarged ventricles (lateral cerebral ventricles) caused by death or a lack of growth of normal brain cells around the ventricles... i believe it is actually the hippocampus that is decreased in size in schizophrenics... i think failure of the hippocampus to filter out information from the cognitive brain centers (neocortex) to the emotional centers (limbic system) can cause overstimulation ....
This is the end of the thread.
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