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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 grapebubblegum on August 16, 2001, at 8:34:31
This is beyond me, but I cut and pasted this, and I am interested in an interpretation from someone who speaks this language. Most specifically, does this tell you anything about how this medication (Geodon) works for anxiety and/or depression as compared to some of the more traditional medications like the various SSRIs and the benzodiazepines?
"Ziprasidone has a high affinity for dopamine type 2 (D2) receptors and substantially higher affinity for serotonin type 2A (5HT2A) receptors. Ziprasidone also interacts with serotonin 5HT2C, 5HT1D and 5HT1A receptors where its affinities for these sites are equal to or greater than its affinity for the D2 receptor. Ziprasidone has moderate affinity for neuronal serotonin and norepinephrine transporters. Ziprasidone demonstrates moderate affinity for histamine H(1)- and alpha(1)-receptors. Antagonism at these receptors has been associated with somnolence and orthostatic hypotension, respectively. Ziprasidone demonstrates negligible affinity for muscarinic M(1)-receptors. Antagonism at this receptor has been associated with memory impairment."
Thanks, Geeb (who sometimes asks hard questions. ;o)
Posted by SalArmy4me on August 16, 2001, at 12:57:48
In reply to Can someone interpret this?, posted by grapebubblegum on August 16, 2001, at 8:34:31
Site of Action - Consequences of Blockade
Histamine-1 receptor - Sedation, antipruritic effect
Muscarinic acetylcholine receptor - Dry mouth, constipation, sinus tachycardia, memory impairment
Norepinephrine (NE) uptake pump - Antidepressant efficacy, increased blood pressure, tremors, diaphoresis
Serotonin (5HT2) uptake pump - Antidepressant efficacy, nausea, loose stools, insomnia, anorgasmia
5-HT2A receptor - Antidepressant efficacy, increased REM sleep, anti-anxiety efficacy, anti-EPS
Alpha-1 NE receptor - Orthostatic hypotension, sedation
5-HT2C receptor - Anti-anxiety efficacy, increased appetite, decreased motor restlessness
5-HT3C receptor - Antinauseant
Alpha-2 NE receptor - Antidepressant efficacy, arousal, increased libido
Sodium fast channels - Delayed repolarization leading to arrhythmias, seizures, delirium
Posted by grapebubblegum on August 16, 2001, at 16:37:55
In reply to Re: Can someone interpret this? » grapebubblegum, posted by SalArmy4me on August 16, 2001, at 12:57:48
Thanks for the mini-dictionary, Sal. I'll have to jot all of that down for comparative purposes.
Posted by grapebubblegum on August 17, 2001, at 20:14:11
In reply to Re: Can someone interpret this?, posted by grapebubblegum on August 16, 2001, at 16:37:55
Just trying to promote this thread in case anyone else has any insight.
Posted by Mitch on August 18, 2001, at 10:18:11
In reply to Can someone interpret this?, posted by grapebubblegum on August 16, 2001, at 8:34:31
> This is beyond me, but I cut and pasted this, and I am interested in an interpretation from someone who speaks this language. Most specifically, does this tell you anything about how this medication (Geodon) works for anxiety and/or depression as compared to some of the more traditional medications like the various SSRIs and the benzodiazepines?
Geodon is an anti-psychotic which is primarily intended for use to control psychotic symptoms and its primary use is for psychotic manifestations resulting from schizophrenia. The primary action of anti-psychotics is to "block" or antagonize dopamine receptors to reduce symptoms of psychosis (esp. the "D2" receptor). The 2nd generation of anti-psychotics (so-called "atypical antipsychotics") have this property but in addition "block" or antagaonize serotonin (5-HT) receptors. This generally reduces adverse symptoms related to blocking the dopamine receptors (such as Parkinsonism-EPS, etc.) Also, this tends to reduce depression related to psychosis with resulting improved social functioning for psychotic patients which was first demonstrated with Clozapine.
Conventional and atypical AP's have also been used to control acute manic states. Chronic use of AP's can result in tardive dystonia or tardive dyskinesia (permanent movement disorders) and they should only be used when other treatments have failed. Low doses of conventional AP's have been used in the past to treat anxiety disorders (such as Mellaril-thioridazine). There is currently no indication for atypical AP's for use in nonpsychotic depression or anxiety disorders.
The other receptors mentioned below are also receptors which are affected by the older conventional AP's such as thorazine, i.e.>
> "Ziprasidone has a high affinity for dopamine type 2 (D2) receptors and substantially higher affinity for serotonin type 2A (5HT2A) receptors. Ziprasidone also interacts with serotonin 5HT2C, 5HT1D and 5HT1A receptors where its affinities for these sites are equal to or greater than its affinity for the D2 receptor. Ziprasidone has moderate affinity for neuronal serotonin and norepinephrine transporters. Ziprasidone demonstrates moderate affinity for histamine H(1)- and alpha(1)-receptors. Antagonism at these receptors has been associated with somnolence and orthostatic hypotension, respectively. Ziprasidone demonstrates negligible affinity for muscarinic M(1)-receptors. Antagonism at this receptor has been associated with memory impairment."
>
> Thanks, Geeb (who sometimes asks hard questions. ;o)
Posted by grapebubblegum on August 19, 2001, at 17:05:19
In reply to Re: Can someone interpret this? » grapebubblegum, posted by Mitch on August 18, 2001, at 10:18:11
Thanks, Mitch. That really does help my understanding.
Posted by Sherry on August 19, 2001, at 19:23:10
In reply to Re: Can someone interpret this? » grapebubblegum, posted by Mitch on August 18, 2001, at 10:18:11
The primary action of anti-psychotics is to "block" or antagonize dopamine receptors to reduce symptoms of psychosis (esp. the "D2" receptor). The 2nd generation of anti-psychotics (so-called "atypical antipsychotics") have this property but in addition "block" or antagaonize serotonin (5-HT) receptors.
Please excuse my ignorance, but all this blocking of receptors sounds like to me it would at least theoretically cause a worsened depression. I thought that depression was caused by a shortage of the NT's binding to receptors. Am I way off base?
Sherry
Posted by grapebubblegum on August 19, 2001, at 21:11:43
In reply to Re: Can someone interpret this?, posted by Sherry on August 19, 2001, at 19:23:10
Well, I think that at least in the case of the NT's being discussed, the depression is supposedly caused by a shortage of NT in the synapse. Therefore, if the NT in question is blocked from being reabsorbed, it spends more time in the synaptic cleft than it would have without the "blockade." The theory being that in some cases depressed people MAKE enough of a certain neurotransmittor but then it is taken up too quickly or in too great a number at the other side of the synapse. Think of a tennis ball shooting machine being the first part of the synapse and some tennis court attendants picking up those balls being the other side of the synapse. The blockade or reuptake inhibition would be the benching of some of those attendants so that the tennis balls can spend some time on the court (the synaptic cleft, as my analogy goes) instead of being snatched right up.
My standard disclaimer of "pardon my ignorance" goes too, in case I am wrong; that is just my rough understanding.
Posted by Cam W. on August 20, 2001, at 10:43:00
In reply to Re: Can someone interpret this?, posted by grapebubblegum on August 19, 2001, at 21:11:43
GBG & Sherry - Actually, the lack of neurotransmitter is not a cause, but a symptom (or an effect) of depression. If you naturally deplete serotonin (using a tryptophan-free amino acid drink) from a healthy, non-depressed individual, nothing happens. But, if you deplete serotonin from some people who have had depression and are in remission, they will relapse.
There is something going on in away from the serotonin (&/or norepinephrine, dopamine, etc) receptor that is causing this decrease in neurotransmitter. This may be at the level of second messengers &/or genetic transcription within the cell, or may be in a different system from the body's stress mechanism (HPA axis), such as the immune system (involving cytokine concentrations) or at the level of the hippocampus, amygdala, or other related brain structure.
Scientists are beginning to tease apart these systems, so we should have some answers within the next few years. I believe that the monoamine theory of depression is starting to look "dead in the water".
My 2¢ - Cam
Posted by Sherry on August 20, 2001, at 17:55:36
In reply to Re: Can someone interpret this? » grapebubblegum, posted by Cam W. on August 20, 2001, at 10:43:00
Thanks for the info. I am trying my best to learn, but finding it very difficult. I think I would have done much better before depression. Great analogy GBG. Really helped me understand. Cam what is the monoamine theory of depression?
> GBG & Sherry - Actually, the lack of neurotransmitter is not a cause, but a symptom (or an effect) of depression. If you naturally deplete serotonin (using a tryptophan-free amino acid drink) from a healthy, non-depressed individual, nothing happens. But, if you deplete serotonin from some people who have had depression and are in remission, they will relapse.
>
> There is something going on in away from the serotonin (&/or norepinephrine, dopamine, etc) receptor that is causing this decrease in neurotransmitter. This may be at the level of second messengers &/or genetic transcription within the cell, or may be in a different system from the body's stress mechanism (HPA axis), such as the immune system (involving cytokine concentrations) or at the level of the hippocampus, amygdala, or other related brain structure.
>
> Scientists are beginning to tease apart these systems, so we should have some answers within the next few years. I believe that the monoamine theory of depression is starting to look "dead in the water".
>
> My 2¢ - Cam
Posted by Cam W. on August 20, 2001, at 23:47:30
In reply to Re: Can someone interpret this? Cam and GBG, posted by Sherry on August 20, 2001, at 17:55:36
Sherry - In a nutshell, the monoamine theory of depression is that a shortage of serotonin, norpinephrine, or dopamine (monoamines) "causes" depression. We now think that the real cause is something else, and that the monoamine shortage is a result of the real cause of depression. - Cam
Posted by Zo on August 21, 2001, at 21:31:59
In reply to Re: Can someone interpret this? » grapebubblegum, posted by Cam W. on August 20, 2001, at 10:43:00
Cam,
You're going to think I oversimplified, if you come across my dopamine post on another thread. . .
For purposes of med discussion, I'm still referring to it as a dopamine deficiency. . .but thanks for putting in that reminder of how it really works.
Incidentally, I am so sensitive to cytokine depression, I get suicidal if I get the flu. . so I get flu shots. . .and pray!
Zo
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