![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by SLS on April 24, 2004, at 12:40:26
Does anyone know the mechanism(s) by which Nardil and Parnate produce hypotension. I'm drawing a blank, and I'm too lazy to go Googling today. Maybe NE alpha-1 antagonism?
Thanks.
- Scott
Posted by djmmm on April 24, 2004, at 19:10:22
In reply to MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 12:40:26
> Does anyone know the mechanism(s) by which Nardil and Parnate produce hypotension. I'm drawing a blank, and I'm too lazy to go Googling today. Maybe NE alpha-1 antagonism?
>
> Thanks.
>
>
> - Scott
I think you are right..it's due to alpha receptor antagonism
Posted by SLS on April 24, 2004, at 19:25:41
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by djmmm on April 24, 2004, at 19:10:22
Thanks.
:-)
Posted by SLS on April 24, 2004, at 21:14:35
In reply to Re: MAOI causes hypotension - What's the mechanism? » djmmm, posted by SLS on April 24, 2004, at 19:25:41
OK. It looks like we were both wrong - at least according to what little I could find on the Net. I wish I could have found something more definitive, though. Maybe you'll have better luck.
I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
http://www.acnp.org/g4/GN401000046/CH046.html
----------------------------------------------------------
SIDE EFFECTS OF MAOIS
Orthostatic HypotensionOrthostatic hypotension is a common side effect of the irreversible MAOIs, particularly phenelzine (Table 4). Clinically, the development of orthostatic symptoms is gradual and appears generally after 2–3 weeks of treatment. The relationship of the time course of this response to the etiology of orthostasis remains unclear. Some have suggested it may represent a compensatory down-regulation of peripheral ganglionic effects in response to central sympathetic stimulation. Others have proposed that inhibition of amine metabolism results in an artificial, supraphysiologic elevation of amines with few or no pressor effects and the resultant replacement of amines with greater pressor effects from intracellular amine stores. Gradual accumulation of octopamine in adrenergic neurons, for instance, may be the result of MAO inhibition and resultant alternate hydroxylation of tyramine to octopamine. It has been suggested that octopamine may replace NE from intra-axonal storage granules. Octopamine released upon sympathetic stimulation may act as a 'false neurotransmitter' with minimal activity at a- or b-adrenergic receptors. The result is a functional block of sympathetic neurotransmission, accompanied by decreased ability to regulate blood pressure in response to postural changes.
----------------------------------------------------------
- Scott
Posted by chemist on April 24, 2004, at 23:36:22
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 21:14:35
> OK. It looks like we were both wrong - at least according to what little I could find on the Net. I wish I could have found something more definitive, though. Maybe you'll have better luck.
>
> I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
>
> http://www.acnp.org/g4/GN401000046/CH046.html
>
>
> ----------------------------------------------------------
>
>
> SIDE EFFECTS OF MAOIS
>
>
> Orthostatic Hypotension
>
> Orthostatic hypotension is a common side effect of the irreversible MAOIs, particularly phenelzine (Table 4). Clinically, the development of orthostatic symptoms is gradual and appears generally after 2–3 weeks of treatment. The relationship of the time course of this response to the etiology of orthostasis remains unclear. Some have suggested it may represent a compensatory down-regulation of peripheral ganglionic effects in response to central sympathetic stimulation. Others have proposed that inhibition of amine metabolism results in an artificial, supraphysiologic elevation of amines with few or no pressor effects and the resultant replacement of amines with greater pressor effects from intracellular amine stores. Gradual accumulation of octopamine in adrenergic neurons, for instance, may be the result of MAO inhibition and resultant alternate hydroxylation of tyramine to octopamine. It has been suggested that octopamine may replace NE from intra-axonal storage granules. Octopamine released upon sympathetic stimulation may act as a 'false neurotransmitter' with minimal activity at a- or b-adrenergic receptors. The result is a functional block of sympathetic neurotransmission, accompanied by decreased ability to regulate blood pressure in response to postural changes.
>
> ----------------------------------------------------------
>
>
> - Scottchemist here....monoamineoxidase is an enzyme that is prevalent throughout your body. MAO inhibitors prevent the enzyme from oxidizing chemicals that contain an amino group ( to a nitroxide). this means that anything with a (ordinarily) oxizidable amino group does not get metabolized properly and the substance bulids up in your system. the dietary restrictions - and drug interactions - with MAOIs are most specific for sympathomimetic amines that cause central nervous system stimulation, such as amphetamine (dexedrine, adderall); provigil; methylphenidate; and other amino-rich substances. the interaction with ssris is that many of them block reuptake of norepinephrine, dopamine, and or course, serotonin. the trouble comes when you are on an MAOI and indulge in one of these substances. the equivalent is that of raising your blood pressure, becuase you have bumped-up the concentratioon of stimulants in yur system. this is why it is advisable to carry 50 mg thorazine with you in case you are slipped something like soy sauce in your meal. hypertension ensues, and this can lead to stoke or, at leasst, very uncomfortable hypertension.....all the best, chemist
Posted by djmmm on April 25, 2004, at 8:06:06
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 21:14:35
> OK. It looks like we were both wrong - at least according to what little I could find on the Net. I wish I could have found something more definitive, though. Maybe you'll have better luck.
>
> I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
>
> http://www.acnp.org/g4/GN401000046/CH046.html
>
>
> ----------------------------------------------------------
>
>
> SIDE EFFECTS OF MAOIS
>
>
> Orthostatic Hypotension
>
> Orthostatic hypotension is a common side effect of the irreversible MAOIs, particularly phenelzine (Table 4). Clinically, the development of orthostatic symptoms is gradual and appears generally after 2–3 weeks of treatment. The relationship of the time course of this response to the etiology of orthostasis remains unclear. Some have suggested it may represent a compensatory down-regulation of peripheral ganglionic effects in response to central sympathetic stimulation. Others have proposed that inhibition of amine metabolism results in an artificial, supraphysiologic elevation of amines with few or no pressor effects and the resultant replacement of amines with greater pressor effects from intracellular amine stores. Gradual accumulation of octopamine in adrenergic neurons, for instance, may be the result of MAO inhibition and resultant alternate hydroxylation of tyramine to octopamine. It has been suggested that octopamine may replace NE from intra-axonal storage granules. Octopamine released upon sympathetic stimulation may act as a 'false neurotransmitter' with minimal activity at a- or b-adrenergic receptors. The result is a functional block of sympathetic neurotransmission, accompanied by decreased ability to regulate blood pressure in response to postural changes.
>
> ----------------------------------------------------------
>
>
> - ScottI too came across that link, however I found several more indicating that it is the antagonism of adrenergic receptors..so who knows...but I do know that severe hypotension (associated with overdose) is often treated with Levophed (norepinephrine) because this med stimulates alpha and beta adrenergic receptors.
Posted by SLS on April 25, 2004, at 8:31:51
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by djmmm on April 25, 2004, at 8:06:06
> > I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
> > http://www.acnp.org/g4/GN401000046/CH046.html> I too came across that link, however I found several more indicating that it is the antagonism of adrenergic receptors..so who knows...but I do know that severe hypotension (associated with overdose) is often treated with Levophed (norepinephrine) because this med stimulates alpha and beta adrenergic receptors.
It never ceases to amaze me how little research has been performed toward elucidating the mysteries of a class of drugs that have been around for over 40 years.
Thanks for taking the time.
:-)
- Scott
Posted by King Vultan on April 25, 2004, at 10:03:37
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 21:14:35
> OK. It looks like we were both wrong - at least according to what little I could find on the Net. I wish I could have found something more definitive, though. Maybe you'll have better luck.
>
> I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
>
> http://www.acnp.org/g4/GN401000046/CH046.html
>
>
> ----------------------------------------------------------
>
>
> SIDE EFFECTS OF MAOIS
>
>
> Orthostatic Hypotension
>
> Orthostatic hypotension is a common side effect of the irreversible MAOIs, particularly phenelzine (Table 4). Clinically, the development of orthostatic symptoms is gradual and appears generally after 2–3 weeks of treatment. The relationship of the time course of this response to the etiology of orthostasis remains unclear. Some have suggested it may represent a compensatory down-regulation of peripheral ganglionic effects in response to central sympathetic stimulation. Others have proposed that inhibition of amine metabolism results in an artificial, supraphysiologic elevation of amines with few or no pressor effects and the resultant replacement of amines with greater pressor effects from intracellular amine stores. Gradual accumulation of octopamine in adrenergic neurons, for instance, may be the result of MAO inhibition and resultant alternate hydroxylation of tyramine to octopamine. It has been suggested that octopamine may replace NE from intra-axonal storage granules. Octopamine released upon sympathetic stimulation may act as a 'false neurotransmitter' with minimal activity at a- or b-adrenergic receptors. The result is a functional block of sympathetic neurotransmission, accompanied by decreased ability to regulate blood pressure in response to postural changes.
>
> ----------------------------------------------------------
>
>
> - Scott
Wow, is that complicated--I think I'd have to do quite a bit of research in order to come to some type of opinion as to what is actually going on. I think we also need to take into account the common reduction in heart rate also, which one would think is related somehow. My BP has gone down about 30/20, and my pulse has decreased about 20 bpm since going on Nardil.I've been on the tricyclics also, which also made my BP go down but caused my heart rate to increase. Here, it seems clear that the decrease in BP is due to alpha-1 antagonism. Preskorn (www.preskorn.com) says that desipramine does not blockade the alpha-1 adrenergic receptor, but my BP definitely went down as I increased the dosage, and then went up as I came off the med. I also take an alpha-1 blocker for a minor prostate condition and found I had to increase the dosage as I came off the desipramine.
The increase in heart rate I noticed on tricyclics appears to be due to blockade of norepinephrine reuptake and subsequent stimulation of beta adrenergic receptors. There is a concurrent tendency to increase blood pressure from this effect also, but at least in my case, the alpha-1 antagonism won out, and I had a net decrease in BP, at least at higher dosages. Some people do experience an increase in BP on tricyclics, but I think this is more common on drugs that block NE reuptake but do not have an alpha-1 blockade, such as Effexor.
Todd
Posted by zeugma on April 25, 2004, at 10:19:25
In reply to Re: MAOI causes hypotension - What's the mechanism? » SLS, posted by King Vultan on April 25, 2004, at 10:03:37
I experienced a lowering in blood pressure on nortriptyline, which necessitated an extended titration schedule. I was very sensitive to the hypotensive properties of the TCA.
Posted by SLS on April 25, 2004, at 10:39:27
In reply to Re: MAOI causes hypotension - What's the mechanism? » SLS, posted by King Vultan on April 25, 2004, at 10:03:37
Hi Todd.
Nardil sure is a weird drug, isn't it? My heart rate decreases also, especially at dosages of 75mg and higher. As far as blood pressure is concerned, it plummeted to the point of my not being able to stand up when I added imipramine to it. However, I found that adding desipramine potentiated the hypotensive effect of Nardil to only a modest degree. Preskorn is something, isn't he?
As I described in another thread, I experienced a hypotensive crisis when starting clorgyline after pretreatment with idazoxan. I wrote in that post that I thought my BP was between 30-35 mm Hg. Actually, it was in the 20s during the hypotensive episode. Like you, my pressure every day at the NIH was in in the low 30s for the many weeks that I took clorgyline. They didn't understand how I was able to walk upright.
- Scott
Posted by SLS on April 25, 2004, at 11:16:28
In reply to Re: MAOI causes hypotension - What's the mechanism? » SLS, posted by King Vultan on April 25, 2004, at 10:03:37
Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
imipramine
desipramine
amitriptyline
nortriptyline
phenelzine
tranylcypromine
fluoxetine
sertraline
paroxetine
venlafaxine
bupropion
mirtazapine
Thanks. I know it's a lot, but I tried to keep it to a minimum. Of course, if you would like to add more, I wouldn't complain! :-) I would love to find this book at the book store to see if it is worth buying. What do you think? Unfortunately, money is an issue. The first book I would consider investing in would be one of Stephen Stahl's Essential Pharmacology books. I'm not sure which one to get though.There's "Essential Psychopharmacology : Neuroscientific Basis and Practical Applications" and "Essential Psychopharmacology of Depression and Bipolar Disorder"
This is the first time I'm using the double quote feature. I hope it works.
- Scott
Posted by King Vultan on April 25, 2004, at 18:30:30
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by SLS on April 25, 2004, at 10:39:27
> Hi Todd.
>
> Nardil sure is a weird drug, isn't it? My heart rate decreases also, especially at dosages of 75mg and higher. As far as blood pressure is concerned, it plummeted to the point of my not being able to stand up when I added imipramine to it. However, I found that adding desipramine potentiated the hypotensive effect of Nardil to only a modest degree. Preskorn is something, isn't he?
>
> As I described in another thread, I experienced a hypotensive crisis when starting clorgyline after pretreatment with idazoxan. I wrote in that post that I thought my BP was between 30-35 mm Hg. Actually, it was in the 20s during the hypotensive episode. Like you, my pressure every day at the NIH was in in the low 30s for the many weeks that I took clorgyline. They didn't understand how I was able to walk upright.
>
>
> - ScottActually, I meant that my blood pressure had decreased by 30/20 from normal, which is 140/90 for me, so my net BP is about 110/70. MAOIs and tricyclics, in general, do seem to be good drugs for people with hypertension to take. I just eliminated my lisinopril ACE inhibitor Friday because of hypotension with the Nardil, especially after climbing stairs.
So are you saying that your BP was actually in the 20's or 30's? Holy cow, that is so low that I would have thought it was incompatible with human life. What is the lowest your BP has ever been measured at, with the top and bottom numbers? The lowest I ever saw on desipramine (and 10-20 mg lisinopril) was 90/59, but with a heart rate of 99, my total cardiac output was high enough that it was not a severe problem. On 75 mg/day Nardil, with a trivial 5 mg of lisinopril, a recent reading was 108/69 with a pulse of 50. The total cardiac output is so low that it is causing me a fair amount of problems; although, I haven't fainted yet. I just increased the dosage of Nardil to 90 mg/day and hope the BP and heart rate do not decline much further. But comparing my situation to the one you were describing, I appear to be a bit of a wuss.
Todd
Posted by fires on April 25, 2004, at 18:31:40
In reply to MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 12:40:26
I'm sure someone answered the question by now. I didn't take the time to read all of the posts to see if anyone oferred you a possible solution.>>> When I was on Parnate , 60-70 mg per day, the only thing that allowed me to stay on it, without severe OH, was 20 mg of Reglan/day. My Doc was one of few who seemed to know of this use for Reglan. I never did learn why it works.
Bye
Posted by King Vultan on April 25, 2004, at 18:56:38
In reply to Re: MAOI causes hypotension - What's the mechanism? » King Vultan, posted by SLS on April 25, 2004, at 11:16:28
> Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
>
> imipramine
> desipramine
> amitriptyline
> nortriptyline
> phenelzine
> tranylcypromine
> fluoxetine
> sertraline
> paroxetine
> venlafaxine
> bupropion
> mirtazapine
>
>
> Thanks. I know it's a lot, but I tried to keep it to a minimum. Of course, if you would like to add more, I wouldn't complain! :-) I would love to find this book at the book store to see if it is worth buying. What do you think? Unfortunately, money is an issue. The first book I would consider investing in would be one of Stephen Stahl's Essential Pharmacology books. I'm not sure which one to get though.
>
> There's "Essential Psychopharmacology : Neuroscientific Basis and Practical Applications" and "Essential Psychopharmacology of Depression and Bipolar Disorder"
>
> This is the first time I'm using the double quote feature. I hope it works.
>
>
> - ScottUnfortunately, "Psychotropic Drugs" does not have the actual Ki values but rather has one of those charts with +'s, with the +'s based off the actual Ki values from those two classic studies. I like the chart because it lists a fairly wide variety of drugs and the receptor affinities cover seven orders of magnitude, but it is not as good as having the actual numbers. Some people, such as my pdoc, would also take at least some exception to it because it is based off of rodent data, and apparently there are some newer studies involving cloned human cells that may be better. I do have access to a study with actual Ki values for some of the drugs you mentioned that are in either rodent or human cadaver tissue, depending on the receptor. I can try to post the info tomorrow you asked for.
Of the books you mentioned, "Essential Psychopharmacology" is truly excellent, and I have learned just a ton of things from reading it. The easy to read diagrams make it a good choice for the interested layman, while there is also enough detail to be valuable to even professionals, I believe. It seems clear from some of the anecdotes I've read here that there are doctors out there who could do with a careful reading of this book.
Todd
Posted by SLS on April 25, 2004, at 19:26:53
In reply to Re: MAOI causes hypotension - What's the mechanism? » SLS, posted by King Vultan on April 25, 2004, at 18:30:30
> So are you saying that your BP was actually in the 20's or 30's? Holy cow, that is so low that I would have thought it was incompatible with human life.
To tell you the truth, my memory is not very clear about what went on with me back then. I think my diastolic BP dropped below 30 briefly and then remained around 40 thereafter. I'm really not sure, but when a new technician took my BP for the first time, he would get pretty upset looking at the numbers and have to verify with the nursing staff that I was not dying.
- Scott
Posted by chemist on April 26, 2004, at 0:05:46
In reply to Re: MAOI causes hypotension - What's the mechanism? » SLS, posted by King Vultan on April 25, 2004, at 18:56:38
chemist here...see my comments denoted by ***
> > Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
> >
> > imipramine
** IC_{50} @ 0.54 micromolar on 5-HT-{3}*****
**** k_{i} @ 1 nanomolar for potassium-regulated reuptake ******
***inhibits human parotid @ 102 nanomolar ****
> > desipramine
*** inhibits paroxetine @ 4.4 nanomolar ****
*** inhibits parotid @ 135 nanomolar ****
> > amitriptyline
> > nortriptyline
> > phenelzine
**** IC_{50} @ 4.2 micromolar on 5-HT_{3}***
> > tranylcypromine
> > fluoxetine
**** IC_{50} @ 1.3 micromolaron 5-HT_{3} ****
*** inhibits binding of paroxetine @ 3 nanomolar
> > sertraline
**** K_{D} 0.57 nanomolar to 3.4 nanomolar in comparison to NE uptake**** (!!!) *****
> > paroxetine
***inhibits CYP2D6 @ 0.15 micromolar conc.***
*** inhibits @ 0.73 nanomolar in comp. to NE ***
> > venlafaxine
**** K_{i} for NE @ 1.26 micormolar, @ 74 nanomolar for 5-HT ****
> > bupropion
> > mirtazapine
> >
> >
> > Thanks. I know it's a lot, but I tried to keep it to a minimum. Of course, if you would like to add more, I wouldn't complain! :-) I would love to find this book at the book store to see if it is worth buying. What do you think? Unfortunately, money is an issue. The first book I would consider investing in would be one of Stephen Stahl's Essential Pharmacology books. I'm not sure which one to get though.
> >
> > There's "Essential Psychopharmacology : Neuroscientific Basis and Practical Applications" and "Essential Psychopharmacology of Depression and Bipolar Disorder"
> >
> > This is the first time I'm using the double quote feature. I hope it works.
> >
> >
> > - Scott
>
> Unfortunately, "Psychotropic Drugs" does not have the actual Ki values but rather has one of those charts with +'s, with the +'s based off the actual Ki values from those two classic studies. I like the chart because it lists a fairly wide variety of drugs and the receptor affinities cover seven orders of magnitude, but it is not as good as having the actual numbers. Some people, such as my pdoc, would also take at least some exception to it because it is based off of rodent data, and apparently there are some newer studies involving cloned human cells that may be better. I do have access to a study with actual Ki values for some of the drugs you mentioned that are in either rodent or human cadaver tissue, depending on the receptor. I can try to post the info tomorrow you asked for.
>
> Of the books you mentioned, "Essential Psychopharmacology" is truly excellent, and I have learned just a ton of things from reading it. The easy to read diagrams make it a good choice for the interested layman, while there is also enough detail to be valuable to even professionals, I believe. It seems clear from some of the anecdotes I've read here that there are doctors out there who could do with a careful reading of this book.
>
> Toddbest, chemist
Posted by chemist on April 26, 2004, at 0:40:10
In reply to Re: MAOI causes hypotension - What's the mechanism? » King Vultan, posted by chemist on April 26, 2004, at 0:05:46
chemist again....as you know, you can extract K_{i} from K_{M}, for which there are more data...use the lineweaver-burk method....or, alternatively, look at k_{1} in addition to the michalis-menten constant...assuming the usuals for m-m enzyme-substrate specificity...and you will get competitive K_{i}....all the best, chemist
> chemist here...see my comments denoted by ***
>
> > > Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
> > >
> > > imipramine
> ** IC_{50} @ 0.54 micromolar on 5-HT-{3}*****
> **** k_{i} @ 1 nanomolar for potassium-regulated reuptake ******
> ***inhibits human parotid @ 102 nanomolar ****
> > > desipramine
> *** inhibits paroxetine @ 4.4 nanomolar ****
> *** inhibits parotid @ 135 nanomolar ****
> > > amitriptyline
> > > nortriptyline
> > > phenelzine
> **** IC_{50} @ 4.2 micromolar on 5-HT_{3}***
> > > tranylcypromine
> > > fluoxetine
> **** IC_{50} @ 1.3 micromolaron 5-HT_{3} ****
> *** inhibits binding of paroxetine @ 3 nanomolar
> > > sertraline
> **** K_{D} 0.57 nanomolar to 3.4 nanomolar in comparison to NE uptake**** (!!!) *****
> > > paroxetine
> ***inhibits CYP2D6 @ 0.15 micromolar conc.***
> *** inhibits @ 0.73 nanomolar in comp. to NE ***
> > > venlafaxine
> **** K_{i} for NE @ 1.26 micormolar, @ 74 nanomolar for 5-HT ****
> > > bupropion
> > > mirtazapine
> > >
> > >
> > > Thanks. I know it's a lot, but I tried to keep it to a minimum. Of course, if you would like to add more, I wouldn't complain! :-) I would love to find this book at the book store to see if it is worth buying. What do you think? Unfortunately, money is an issue. The first book I would consider investing in would be one of Stephen Stahl's Essential Pharmacology books. I'm not sure which one to get though.
> > >
> > > There's "Essential Psychopharmacology : Neuroscientific Basis and Practical Applications" and "Essential Psychopharmacology of Depression and Bipolar Disorder"
> > >
> > > This is the first time I'm using the double quote feature. I hope it works.
> > >
> > >
> > > - Scott
> >
> > Unfortunately, "Psychotropic Drugs" does not have the actual Ki values but rather has one of those charts with +'s, with the +'s based off the actual Ki values from those two classic studies. I like the chart because it lists a fairly wide variety of drugs and the receptor affinities cover seven orders of magnitude, but it is not as good as having the actual numbers. Some people, such as my pdoc, would also take at least some exception to it because it is based off of rodent data, and apparently there are some newer studies involving cloned human cells that may be better. I do have access to a study with actual Ki values for some of the drugs you mentioned that are in either rodent or human cadaver tissue, depending on the receptor. I can try to post the info tomorrow you asked for.
> >
> > Of the books you mentioned, "Essential Psychopharmacology" is truly excellent, and I have learned just a ton of things from reading it. The easy to read diagrams make it a good choice for the interested layman, while there is also enough detail to be valuable to even professionals, I believe. It seems clear from some of the anecdotes I've read here that there are doctors out there who could do with a careful reading of this book.
> >
> > Todd
>
>
>
> best, chemist
Posted by SLS on April 26, 2004, at 6:36:51
In reply to Re: MAOI causes hypotension - What's the mechanism? » chemist, posted by chemist on April 26, 2004, at 0:40:10
> ....as you know, you can extract K_{i} from K_{M}, for which there are more data...use the lineweaver-burk method....or, alternatively, look at k_{1} in addition to the michalis-menten constant...assuming the usuals for m-m enzyme-substrate specificity...and you will get competitive K_{i}....
Of course I know! We learned that stuff back in the fourth grade!
:-) <chuckle>
I'm not quite that well educated, so I will defer to you whenever such extractions are necessary. Thanks chemist. Your expertise is certainly welcome here. :-)
- Scott
Posted by chemist on April 26, 2004, at 11:47:51
In reply to Re: MAOI causes hypotension - What's the mechanism? » chemist, posted by SLS on April 26, 2004, at 6:36:51
> > ....as you know, you can extract K_{i} from K_{M}, for which there are more data...use the lineweaver-burk method....or, alternatively, look at k_{1} in addition to the michalis-menten constant...assuming the usuals for m-m enzyme-substrate specificity...and you will get competitive K_{i}....
>
> Of course I know! We learned that stuff back in the fourth grade!
>
> :-) <chuckle>
>
> I'm not quite that well educated, so I will defer to you whenever such extractions are necessary. Thanks chemist. Your expertise is certainly welcome here. :-)
>
>
> - Scott
>good one, scott...made my morning.....i will dig up the numbers you need as i riffle through my literature.....needless to say, not much for competitive binding in presence of NE - which i think is what the post was originally asking for - but a few in comparison to NE.....anyways, back to the books! all the best, chemist
Posted by King Vultan on April 26, 2004, at 12:46:02
In reply to Re: MAOI causes hypotension - What's the mechanism? » King Vultan, posted by SLS on April 25, 2004, at 11:16:28
> Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
>
> imipramine
> desipramine
> amitriptyline
> nortriptyline
> phenelzine
> tranylcypromine
> fluoxetine
> sertraline
> paroxetine
> venlafaxine
> bupropion
> mirtazapine
>
>Sorry, I only have half of the ones you listed:
------------------------Ki
---------------------Alpha-1
------------------Human cortex
---------------(cadaver tissue used)amitriptyline..........4.4 +/- 0.2
desipramine............23 +/- 1
paroxetine.............995 +/- 35
sertraline................36 +/- 2
fluoxetine............1353 +/- 17
venlafaxine........39921 +/- 810FWIW, it also lists
nefazodone.............5.5 +/- 0.3
trazodone................12 +/- 0.2As a comparison, phentolamine is listed as 3.4
Todd
Posted by SLS on April 26, 2004, at 13:16:34
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by King Vultan on April 26, 2004, at 12:46:02
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.