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        Cluster Headache Help and Support >> Medications, Treatments, Therapies >> CGRP Inhibition and Topiramate
        
(Message started by: Lizzie2 on Oct 14^th, 2006, 10:42pm)

Title: CGRP Inhibition and Topiramate
Post by Lizzie2 on Oct 14^th, 2006, 10:42pm

I know that topiramate (topamax, dopeymax) is a drug that many here absolutely hate, but I came across an article that was published in one of the more recent editions of "Headache" (the journal of the American Headache Society) about how topiramate works with respect to migraine prevention. Many times, when we take a preventive for clusters (or migraine or any headache really), the mechanism for how it actually works is unknown. Some of these antiseizure meds have completely unknown mechanisms of action altogether! So, some people looked into how topiramate may be preventing migraine and cluster, and a few different articles have shown that it may work through inhibiting CGRP (calcitonin gene-related peptide).

Before I post the article abstract, here is what Jonathan (Floridian) has written on his site about CGRP, and within his blurb, there is a link to another article that ties topiramate to CGRP inhibition that was published in September 2005. The link for the following is:
http://www.med-owl.com/clusterheadaches/tiki-index.php?page=CGRP

Quote:

CGRP is a chemical in the body associated with the pain of cluster headache and migraine. Researchers have identified some compounds that block CGRP production and act as headache abortives. These compounds are undergoing testing to determine if they are suitable for widespread use. Because they do not have strong vaso-constricting action, CGRP blockers may be useful for individuals that cannot take triptans.

The most widely studied CGRP blocker is referred to as BIBN4096BS. In recent trials, it was 66% effective when given orally. It seems to have both abortive and preventive properties. source (cache)

At least two natural therapies have been shown to reduce CGRP levels. One is Sangre de Grado, or blood of the dragon. The other is a traditional Japanese herbal formula known as Keishi-bukuryo-gan. Although the mechanism of action of these is not fully understood, there is evidence that the oligomeric proanthocyanidins (and possibly anthocyanin plant pigments) are key to the action of Sangre de Grado.

Topiramate (aka Topomax) has been shown to reduce CGRP levels (abstract (cache))

Release of CGRP tends to occur with the release of Substance P, Nitric Oxide and other chemicals that compromise an inflammatory cascade.

And now for the abstract from the latest article about topiramate and CGRP inhibition. While I copied the abstract directly from the Blackwell Synergy website, here is a link on pubmed to see the abstract: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16942474&query_hl=3&itool=pubmed_docsum

Quote:

Headache: The Journal of Head and Face Pain
Volume 46 Page 1291 - September 2006
doi:10.1111/j.1526-4610.2006.00538.x
Volume 46 Issue 8

Brief Communication
Repression of Stimulated Calcitonin Gene-Related Peptide Secretion by Topiramate
Paul L. Durham, PhD; Christine Niemann, PhD; Roger Cady, MD
Objective.—The goal of the proposed research was to determine the effect of topiramate on basal and stimulated release of calcitonin gene-related peptide (CGRP) from trigeminal ganglia neurons.

Background.—CGRP is implicated in migraine headaches. Clinical evidence supports topiramate as an effective migraine prophylactic. In this study, the connection between topiramate and CGRP expression was investigated.

Methods.—Primary cultures of rat trigeminal ganglia were utilized to determine the effects of topiramate on CGRP release stimulated by a depolarizing stimulus (KCl), nitric oxide, and/or protons. The amount of CGRP secreted into the culture media was determined using a CGRP-specific radioimmunoassay.

Results.—Treatment of trigeminal cultures with KCl, nitric oxide donor S-nitroso-N-acetylpenicillamine, or protons (pH 5.5 media) caused a marked increase (3 to 5 fold) in the amount of CGRP release. Topiramate treatment repressed KCl-stimulated CGRP release in a time- and concentration-dependent manner. However, topiramate did not alter the amount of unstimulated or basal CGRP released from trigeminal neurons. In addition, topiramate inhibited nitric oxide and proton mediated CGRP secretion.

Conclusions.—Findings from these studies demonstrate that topiramate can directly repress the stimulated release of CGRP from sensory trigeminal neurons. We propose that topiramate's ability to prevent migraine attacks may involve inhibition of CGRP secretion from trigeminal neurons.

(Headache 2006;46:1291-1295)

If anyone is interested in reading the full-text version of this article, please let me know! I didn't scan all the way through recent med topics, so I hope this hasn't been posted already! If it has been, my apologies!!

Even if you're not a topiramate fan (as I am aware that many are not...), this article is still good because the CGRP inhibitors may be a big help to cluster sufferers at some point down the road, irregardless of whether they are investigating them for migraine or cluster.

PF Wishes,
Carrie :)

Title: Re: CGRP Inhibition and Topiramate
Post by unsolved1 on Oct 14^th, 2006, 11:08pm

That's what Dr. Diamond was talking about (CGRP) . The new preventative drug that she wants me to try (Maybe in January) has something to do with CGRP. It was over my head so I didn't really understand all the technical mumbo-jumbo. I just said ..."Yes, I'll do it"

UNsolved

As soon as I find out the drug name, I'll pass on the info.

Title: Re: CGRP Inhibition and Topiramate
Post by Lizzie2 on Oct 14^th, 2006, 11:12pm

Thanks Unsolved! I saw that thread, but I didn't post to it because I had nothing new to add once people clarified that Trexima wasn't what you were talking about! ;)

I will also keep my ears and eyes open and ask around about a possible med along these lines coming out in the near future - at least for trial!