Re: Re: For anyone interested in the MK-869 thread

[Guest guest]

I don't mean to make it sound like this is going to take the place of

Metrogel or anything, but for those people out there like myself who have

already tried Noritate, Minocycline, Clonidine, Klaron, Plexion, Claritin,

Photoderm, Vitamins, Primrose Oil, skincare adjustments, trigger

avoidance, etc and still have uncontrolled cea I thought this might be a

possible option as far as at least helping a bit.

Admittedly I don't know that much, but I'm basing this on what I've read in

Dr. Nase's book. In his book he says " Medical specialists have demonstrated

that nerve-derived substance P may play a role in skin flushing and rosacea

progression " . He goes on to say that several doctors have used Zofran

successfully to reduce persistent facial redness and flushing in their

patients, and that new oral substance P blockers such as MK-869 may offer

some relief to rosacea sufferers. From my understanding, and from what I

have read in Dr Nase's book, Substance P not only controls some types of

nerve-related pain, but substance P is also a dilator substance that

contributes to blood vessel dilation and skin inflammation. By blocking it,

you may be able to then block certain types of nerve-mediated facial

flushing and inflammation. It is not the only substance in our bodies that

can produce blood vessel dilation, and is not found in unusually high levels

in all cea patients, but it is found to be unusually high in some (the

only study mentioned says 9 out of 23, which comes out to about 40% <-- the

same percentage of people supposedly not finding relief from Metronidazole

products I believe?). I'm not suggesting that this will become the new

mainstream treatment for cea, but I find it hard to believe that I am

the only person who has been unable to find relief with conventional cea

treatment. So for everyone else out there who has been unable to find

relief with the products currently available, I just wanted to let them know

about this one.

I understand this treatment is not being tested for its effectiveness for

cea, but it seems like it Might help. I realize this is not mainstream,

and its not based on trials that show success with thousands of cea

patients. Unfortunately to the best of my knowledge, there are no trials

like that currently going on anywhere in the world. For me, and at least

some of the people on this list we've tried mainstream treatments and they

just haven't worked. If a new medication came out tomorrow that was

indicated for cea and had a proven track record of success, I'd be the

first person lined up to get a prescription, but unfortunately it does not

look like that is going to happen any time soon. So in the meantime I'm

looking for anything that might make it possible to go out and have a normal

day without my skin flushing as soon as i step outside in the sun, or into a

warm room, or eat the wrong food, or try to exercise, or use the wrong soap

etc, and make it possible to sleep without tossing and turning all night

because my cheek hurts too much when pressed up against my pillow... I

mean I wouldn't take some random pill in the hopes that it would cure

cea, but it seems like this one really might help. Sorry for this

turning out to be so long but I guess as I started typing I really needed to

vent. My face has been flushed and in pain for a full 24 hours now, and it

sucks

P.S. I tried the chillow and it was nice, but whenever I took one cheek off

it would start to hurt even worse..like applying Ice.. works temporarily

only

Re: For anyone interested in the MK-869 thread

>

> And I heard Merck's attention is now on another substance P

> inhibitor, but it doesn't matter -- whichever drug they are working

> on, it seemed it is being tested and promoted as an anti-depressant

> that are as safe and effective as the SSRIs but without the sexual

> side effects.

>

> Adam, what's behind your saying that this is " another possible option

> for treating rosacea? " Unless you're holding out on me, I've yet to

> understand how centrally-acting substance P inhibitors could be of

> help to the vast majority of rosaceans. Theoretically, those with

> disabling pain may respond to centrally acting substance p

> inhibitors, which I assume is what Dr. Nase originally was referring

> to. But that's not maintstream rosacea -- my understanding is that

> the burning, stinging and itching of rosacea is usually secondary to

> irritation and inflammation and resolves as those improve. Those

> rosaceans with disabling pain unresponsive to any rosacean treatment

> are best referred to pain control specialists, who specialize in

> managing neurogenic pain.

>

> Marjorie

>

> Marjorie Lazoff, MD

>

>

>

>

>

>

>

>

> > I just came across an article saying Merck began phase III trials

> > for this in the third quarter of 2001, and expect to file for

> > regulatory approval in 2002, so maybe this will be another

> > possible option for treating cea by the end of this year,

> > especially for the people who have depression/anxiety that goes

> > along with it.

> >

> >

> >

> >

[Guest guest]

I know no one's days are normal, and everyone has problems. I just wish I

could focus on typical teenage problems (college, dating, part-time jobs)

etc. without having to worry about how every decision i make affects my

cea (or else I wind up in alot of pain for the rest of the day)

I noticed that the first article you mentioned saying MK-869 was no longer

being studied, appeared in a magazine in 1999 or 2000 (forget which) , and

they began phase III trials in 2001, so the article is outdated, but I am

worried that at one point they discontinued studying it to look for

something with a better side effect profile.. (leads me to believe there are

more side effects than certain articles have been letting on) I understand

what you mean about the differences in a lab vs in the human body. I am

nervous because this is a selective substance-P blocker, that it wont effect

the substance P effectively that contributes to cea.. this was kinda

gonna require a leap of faith (Since unfortunately I'm not quite sure how to

further research that)

In my particular case, I have tried Clonidine for flushing, and it helped a

bit, but thats all. I could try beta-blockers instead, but its my

understanding that they are less effective. Then I tried Photoderm, which i

guess its too early to tell (since I'm still flushing extra from the

treatments) but it doesnt look like that will have been successful either.

As far as I am aware there are no other medications left to try to reduce

flushing. Perhaps in my case there are other medical and/or psychological

issues but I wouldn't know what they are, and I've already seen two doctors,

two derms, an allergist, and a psychiatrist. I didn't mean to make it sound

like I have the worst case of the worst condition in the world or anything,

but anything on the horizon that would offer a little more relief would be

more than welcome

Re: For anyone interested in the MK-869 thread

> Adam, you're right, many small peptides are vasodilators, there's

> nothing special about SP or NO in that regard. But the problem

> confronting all researchers is that there's a big difference between

> how a peptide impacts local tissues in the lab, and how a medication

> that blocks a peptide receptor gets to and impacts local tissue in

> the human body. I know you realize that intellectually.

>

> FYI, here are two abstracts from www.biopsychiatry.com. The first

> abstract says that MK869 is not being studied anymore; the second

> abstract says that centrally acting substance P antagonists (like

> MK869 or Zofran) have not been found effective for pain control

> (although I don't know if either are the final word):

>

> Substance P antagonists:

> novel agents in the treatment of depression

> by

> Argyropoulos SV, Nutt DJ

> Psychopharmacology Unit,

> School of Medical Sciences,

> University Walk, Bristol BS8 1TD, UK.

> spilios.argyropoulos@...

> Expert Opin Investig Drugs 2000 Aug; 9(8):1871-1875

>

> ABSTRACT

> The field of neuropeptides has been expanding very rapidly in recent

> years. Apart from understanding their physiology and elucidating

> their functional role as putative neurotransmitters, research has

> focused on producing drugs that may treat a variety of illnesses in a

> novel way. Substance P antagonists occupy a central role in this area

> of intensive scientific activity. Substance P (SP), an undecapeptide,

> is abundant both in the periphery and in the CNS, where it is usually

> co-localised with one of the classical neurotransmitters, most

> commonly serotonin (5-HT). A role for SP is proposed in the

> regulation of pain, asthma, psoriasis, inflammatory bowel disease

> and, in the CNS, emesis, migraine, schizophrenia, depression and

> anxiety. A recently published positive study of MK 869, in

> depression, a novel SP antagonist has generated excitement amongst

> psychopharmacologists. It is the first time that a drug, not directly

> related to monoamine transmitters, has showed efficacy in depression.

> Although MK 869 has been suspended from further development, a host

> of other compounds, with similar action and better pharmacological

> profile, are currently under development. In this review, the

> pharmacology of central SP and its receptors are discussed, together

> with the exploration of the prospects and implications for future

> treatments of depression.

>

> Discovery of the antidepressant and anti-emetic efficacy of substance

> P receptor (NK1) antagonists

> by

> Rupniak NM, Kramer MS

> Merck Sharp & Dohme Neuroscience Research Centre,

> Harlow, Essex, UK.

> nadia_rupniak@...

> Trends Pharmacol Sci 1999 Dec;20(12):485-90

>

> ABSTRACT

> The development of small-molecule antagonists of the substance P (SP)-

> preferring tachykinin NK1 receptor during the past decade represents

> an important opportunity to exploit these molecules as novel

> therapeutic agents. On the basis of its anatomical localization and

> function, SP has been implicated in diverse pathophysiologies; of

> these, diseases of the CNS have been examined in the greatest detail.

> Although SP is best known as a pain neurotransmitter, it also

> controls vomiting and various behavioural, neurochemical and

> cardiovascular responses to stress. Recent clinical trials have

> confirmed the efficacy of NK1 receptor antagonists to alleviate

> depression and emesis but, surprisingly, not pain. Thus, multiple

> clinical trials, targeted to appropriate patient populations, are

> necessary to define the therapeutic potential of novel

> neurotransmitter ligands.

>

>

> > So in the meantime I'm looking for anything that might make it

> > possible to go out and have a normal

> > day without my skin flushing as soon as i step outside in the sun,

> > or into a warm room, or eat the wrong food, or try to

> > exercise, or use the wrong soap etc, and make it possible to sleep

> > without tossing and turning all night

> > because my cheek hurts too much when pressed up against my

> > pillow... "

>

> I'm not going to victimize you, Adam. I'm seeing you as a man who

> manages his rosacea as best he can, accepts that he's going to flush

> under certain circumstances, and learns to sleep on his back.

>

> On a practical level, if truly none of the medications and treatments

> you listed have done anything for you, there may well be other

> medical and/or psychological issues. For example, you didn't mention

> trying any medications specifically for flushing.

>

> If you're looking for a normal day, forget it -- that's a rumor. No

> day is ever normal, for anyone.

>

> Marjorie

>

> Marjorie Lazoff, MD

>

>

>

>

>

> --

> Please read the list highlights before posting to the whole group

(http://rosacea.ii.net/toc.html). Your post will be delayed if you don't

give a meaningful subject or trim your reply text. You must change the

subject when replying to a digest !

>

> See http://www.drnase.com for info on his recently published book.

>

> To leave the list send an email to

rosacea-support-unsubscribe

>

>

[Guest guest]

I know no one's days are normal, and everyone has problems. I just wish I

could focus on typical teenage problems (college, dating, part-time jobs)

etc. without having to worry about how every decision i make affects my

cea (or else I wind up in alot of pain for the rest of the day)

I noticed that the first article you mentioned saying MK-869 was no longer

being studied, appeared in a magazine in 1999 or 2000 (forget which) , and

they began phase III trials in 2001, so the article is outdated, but I am

worried that at one point they discontinued studying it to look for

something with a better side effect profile.. (leads me to believe there are

more side effects than certain articles have been letting on) I understand

what you mean about the differences in a lab vs in the human body. I am

nervous because this is a selective substance-P blocker, that it wont effect

the substance P effectively that contributes to cea.. this was kinda

gonna require a leap of faith (Since unfortunately I'm not quite sure how to

further research that)

In my particular case, I have tried Clonidine for flushing, and it helped a

bit, but thats all. I could try beta-blockers instead, but its my

understanding that they are less effective. Then I tried Photoderm, which i

guess its too early to tell (since I'm still flushing extra from the

treatments) but it doesnt look like that will have been successful either.

As far as I am aware there are no other medications left to try to reduce

flushing. Perhaps in my case there are other medical and/or psychological

issues but I wouldn't know what they are, and I've already seen two doctors,

two derms, an allergist, and a psychiatrist. I didn't mean to make it sound

like I have the worst case of the worst condition in the world or anything,

but anything on the horizon that would offer a little more relief would be

more than welcome

Re: For anyone interested in the MK-869 thread

> Adam, you're right, many small peptides are vasodilators, there's

> nothing special about SP or NO in that regard. But the problem

> confronting all researchers is that there's a big difference between

> how a peptide impacts local tissues in the lab, and how a medication

> that blocks a peptide receptor gets to and impacts local tissue in

> the human body. I know you realize that intellectually.

>

> FYI, here are two abstracts from www.biopsychiatry.com. The first

> abstract says that MK869 is not being studied anymore; the second

> abstract says that centrally acting substance P antagonists (like

> MK869 or Zofran) have not been found effective for pain control

> (although I don't know if either are the final word):

>

> Substance P antagonists:

> novel agents in the treatment of depression

> by

> Argyropoulos SV, Nutt DJ

> Psychopharmacology Unit,

> School of Medical Sciences,

> University Walk, Bristol BS8 1TD, UK.

> spilios.argyropoulos@...

> Expert Opin Investig Drugs 2000 Aug; 9(8):1871-1875

>

> ABSTRACT

> The field of neuropeptides has been expanding very rapidly in recent

> years. Apart from understanding their physiology and elucidating

> their functional role as putative neurotransmitters, research has

> focused on producing drugs that may treat a variety of illnesses in a

> novel way. Substance P antagonists occupy a central role in this area

> of intensive scientific activity. Substance P (SP), an undecapeptide,

> is abundant both in the periphery and in the CNS, where it is usually

> co-localised with one of the classical neurotransmitters, most

> commonly serotonin (5-HT). A role for SP is proposed in the

> regulation of pain, asthma, psoriasis, inflammatory bowel disease

> and, in the CNS, emesis, migraine, schizophrenia, depression and

> anxiety. A recently published positive study of MK 869, in

> depression, a novel SP antagonist has generated excitement amongst

> psychopharmacologists. It is the first time that a drug, not directly

> related to monoamine transmitters, has showed efficacy in depression.

> Although MK 869 has been suspended from further development, a host

> of other compounds, with similar action and better pharmacological

> profile, are currently under development. In this review, the

> pharmacology of central SP and its receptors are discussed, together

> with the exploration of the prospects and implications for future

> treatments of depression.

>

> Discovery of the antidepressant and anti-emetic efficacy of substance

> P receptor (NK1) antagonists

> by

> Rupniak NM, Kramer MS

> Merck Sharp & Dohme Neuroscience Research Centre,

> Harlow, Essex, UK.

> nadia_rupniak@...

> Trends Pharmacol Sci 1999 Dec;20(12):485-90

>

> ABSTRACT

> The development of small-molecule antagonists of the substance P (SP)-

> preferring tachykinin NK1 receptor during the past decade represents

> an important opportunity to exploit these molecules as novel

> therapeutic agents. On the basis of its anatomical localization and

> function, SP has been implicated in diverse pathophysiologies; of

> these, diseases of the CNS have been examined in the greatest detail.

> Although SP is best known as a pain neurotransmitter, it also

> controls vomiting and various behavioural, neurochemical and

> cardiovascular responses to stress. Recent clinical trials have

> confirmed the efficacy of NK1 receptor antagonists to alleviate

> depression and emesis but, surprisingly, not pain. Thus, multiple

> clinical trials, targeted to appropriate patient populations, are

> necessary to define the therapeutic potential of novel

> neurotransmitter ligands.

>

>

> > So in the meantime I'm looking for anything that might make it

> > possible to go out and have a normal

> > day without my skin flushing as soon as i step outside in the sun,

> > or into a warm room, or eat the wrong food, or try to

> > exercise, or use the wrong soap etc, and make it possible to sleep

> > without tossing and turning all night

> > because my cheek hurts too much when pressed up against my

> > pillow... "

>

> I'm not going to victimize you, Adam. I'm seeing you as a man who

> manages his rosacea as best he can, accepts that he's going to flush

> under certain circumstances, and learns to sleep on his back.

>

> On a practical level, if truly none of the medications and treatments

> you listed have done anything for you, there may well be other

> medical and/or psychological issues. For example, you didn't mention

> trying any medications specifically for flushing.

>

> If you're looking for a normal day, forget it -- that's a rumor. No

> day is ever normal, for anyone.

>

> Marjorie

>

> Marjorie Lazoff, MD

>

>

>

>

>

> --

> Please read the list highlights before posting to the whole group

(http://rosacea.ii.net/toc.html). Your post will be delayed if you don't

give a meaningful subject or trim your reply text. You must change the

subject when replying to a digest !

>

> See http://www.drnase.com for info on his recently published book.

>

> To leave the list send an email to

rosacea-support-unsubscribe

>

>

[Guest guest]

I know no one's days are normal, and everyone has problems. I just wish I

could focus on typical teenage problems (college, dating, part-time jobs)

etc. without having to worry about how every decision i make affects my

cea (or else I wind up in alot of pain for the rest of the day)

I noticed that the first article you mentioned saying MK-869 was no longer

being studied, appeared in a magazine in 1999 or 2000 (forget which) , and

they began phase III trials in 2001, so the article is outdated, but I am

worried that at one point they discontinued studying it to look for

something with a better side effect profile.. (leads me to believe there are

more side effects than certain articles have been letting on) I understand

what you mean about the differences in a lab vs in the human body. I am

nervous because this is a selective substance-P blocker, that it wont effect

the substance P effectively that contributes to cea.. this was kinda

gonna require a leap of faith (Since unfortunately I'm not quite sure how to

further research that)

In my particular case, I have tried Clonidine for flushing, and it helped a

bit, but thats all. I could try beta-blockers instead, but its my

understanding that they are less effective. Then I tried Photoderm, which i

guess its too early to tell (since I'm still flushing extra from the

treatments) but it doesnt look like that will have been successful either.

As far as I am aware there are no other medications left to try to reduce

flushing. Perhaps in my case there are other medical and/or psychological

issues but I wouldn't know what they are, and I've already seen two doctors,

two derms, an allergist, and a psychiatrist. I didn't mean to make it sound

like I have the worst case of the worst condition in the world or anything,

but anything on the horizon that would offer a little more relief would be

more than welcome

Re: For anyone interested in the MK-869 thread

> Adam, you're right, many small peptides are vasodilators, there's

> nothing special about SP or NO in that regard. But the problem

> confronting all researchers is that there's a big difference between

> how a peptide impacts local tissues in the lab, and how a medication

> that blocks a peptide receptor gets to and impacts local tissue in

> the human body. I know you realize that intellectually.

>

> FYI, here are two abstracts from www.biopsychiatry.com. The first

> abstract says that MK869 is not being studied anymore; the second

> abstract says that centrally acting substance P antagonists (like

> MK869 or Zofran) have not been found effective for pain control

> (although I don't know if either are the final word):

>

> Substance P antagonists:

> novel agents in the treatment of depression

> by

> Argyropoulos SV, Nutt DJ

> Psychopharmacology Unit,

> School of Medical Sciences,

> University Walk, Bristol BS8 1TD, UK.

> spilios.argyropoulos@...

> Expert Opin Investig Drugs 2000 Aug; 9(8):1871-1875

>

> ABSTRACT

> The field of neuropeptides has been expanding very rapidly in recent

> years. Apart from understanding their physiology and elucidating

> their functional role as putative neurotransmitters, research has

> focused on producing drugs that may treat a variety of illnesses in a

> novel way. Substance P antagonists occupy a central role in this area

> of intensive scientific activity. Substance P (SP), an undecapeptide,

> is abundant both in the periphery and in the CNS, where it is usually

> co-localised with one of the classical neurotransmitters, most

> commonly serotonin (5-HT). A role for SP is proposed in the

> regulation of pain, asthma, psoriasis, inflammatory bowel disease

> and, in the CNS, emesis, migraine, schizophrenia, depression and

> anxiety. A recently published positive study of MK 869, in

> depression, a novel SP antagonist has generated excitement amongst

> psychopharmacologists. It is the first time that a drug, not directly

> related to monoamine transmitters, has showed efficacy in depression.

> Although MK 869 has been suspended from further development, a host

> of other compounds, with similar action and better pharmacological

> profile, are currently under development. In this review, the

> pharmacology of central SP and its receptors are discussed, together

> with the exploration of the prospects and implications for future

> treatments of depression.

>

> Discovery of the antidepressant and anti-emetic efficacy of substance

> P receptor (NK1) antagonists

> by

> Rupniak NM, Kramer MS

> Merck Sharp & Dohme Neuroscience Research Centre,

> Harlow, Essex, UK.

> nadia_rupniak@...

> Trends Pharmacol Sci 1999 Dec;20(12):485-90

>

> ABSTRACT

> The development of small-molecule antagonists of the substance P (SP)-

> preferring tachykinin NK1 receptor during the past decade represents

> an important opportunity to exploit these molecules as novel

> therapeutic agents. On the basis of its anatomical localization and

> function, SP has been implicated in diverse pathophysiologies; of

> these, diseases of the CNS have been examined in the greatest detail.

> Although SP is best known as a pain neurotransmitter, it also

> controls vomiting and various behavioural, neurochemical and

> cardiovascular responses to stress. Recent clinical trials have

> confirmed the efficacy of NK1 receptor antagonists to alleviate

> depression and emesis but, surprisingly, not pain. Thus, multiple

> clinical trials, targeted to appropriate patient populations, are

> necessary to define the therapeutic potential of novel

> neurotransmitter ligands.

>

>

> > So in the meantime I'm looking for anything that might make it

> > possible to go out and have a normal

> > day without my skin flushing as soon as i step outside in the sun,

> > or into a warm room, or eat the wrong food, or try to

> > exercise, or use the wrong soap etc, and make it possible to sleep

> > without tossing and turning all night

> > because my cheek hurts too much when pressed up against my

> > pillow... "

>

> I'm not going to victimize you, Adam. I'm seeing you as a man who

> manages his rosacea as best he can, accepts that he's going to flush

> under certain circumstances, and learns to sleep on his back.

>

> On a practical level, if truly none of the medications and treatments

> you listed have done anything for you, there may well be other

> medical and/or psychological issues. For example, you didn't mention

> trying any medications specifically for flushing.

>

> If you're looking for a normal day, forget it -- that's a rumor. No

> day is ever normal, for anyone.

>

> Marjorie

>

> Marjorie Lazoff, MD

>

>

>

>

>

> --

> Please read the list highlights before posting to the whole group

(http://rosacea.ii.net/toc.html). Your post will be delayed if you don't

give a meaningful subject or trim your reply text. You must change the

subject when replying to a digest !

>

> See http://www.drnase.com for info on his recently published book.

>

> To leave the list send an email to

rosacea-support-unsubscribe

>

>