Substance P and NK1 Antagonists

[Guest guest]

For anybody who this thread doesn't interest, I'm sorry for so

many posts about it recently, but I just seem to keep finding

stuff that seems really interesting and and relevent to cea

research. Here is an article that talks about Substance P

binding with NK1 receptors (NK1 = Neurokinin, another dilator

substance mentioned in Dr Nases's book) For those who are

interested, It is theorized that Substance P, Nitric Oxide, CGRP,

and Neurokinin A are implicated in cea flushing in response

to skin irritation, heat(My worst trigger by far.. comes in many

different forms), sun, and wind.

For anyone who has followed my previous posts, MK-869 is also a

NK1 receptor antagonist. Unfortunately, from what I've read, it

seems like it primarily just blocks Substance P in the brain (its

being tested as an antidepressant/antianxiety medication) so I

don't know if it will actually block Substance P being produced

at the nerve endings. If anybody has any ideas how we might be

able to find this out, I'd really like to hear them, I am

thinking of contacting Merck and asking them directly if they

might be able to explain it to me a little better. Anyway,

here's the article, its much Shorter than the last ones and maybe

of more interest. I do want to point out though, that Marjorie

is absolutely right in saying all the clinical studies done to

test Substance P blockers' effect on pain were quite

discouraging, so as a pain-reliever this probably will actually

not help cea afterall. I'm hoping it can benefit us by

reducing flushing/inflammation.

Clinical analgesic trials of NK1 antagonists

A Dionne

Current Opinion in CPNS Investigational Drugs 1999 1(1):82-85

Current Drugs Ltd ISSN 1464-844X

The wide distribution of substance P (SP) in the nervous system,

including 45% of the cell bodies of small afferent neurons that

respond to noxious stimuli, and demonstrations that direct

application of SP onto these neurons produces Excitation [1] and

Hyperalgesia [2-4] led to the hypothesis that SP is a mediator of

pain transmission from primary sensory fibers. SP most avidly

binds to the neurokinin-1 (NK1) receptor, found on many spinal

dorsal horn neurons that respond to noxious stimuli [2,5]. In

addition to central postsynaptic effects, SP is released from

peripheral nerve endings and may contribute to Inflammation and

Sensitization of Peripheral Nociceptors by effects such as -

Vasodilatation, increased vascular permeability, and release of

inflammatory mediators from leukocytes and mast cells [6-8] -. SP

has also been implicated in the pain associated with migraine

headaches by release, along with other inflammatory peptides,

from inflamed dura to stimulate NK1 receptors on the dural

vasculature. This spectrum of distribution and activity of SP led

to the development and clinical evaluation of NK1 receptor

antagonists for acute pain, migraine and in inflammation.