CGRP Blockers & SRAs – The New Faces In Research For Migraine Management

CGRP stands for Calcitonin Gene-Related Peptide. It is a calcitonin group compound made up of polymers of amino acid monomers. CGRP is manufactured in the human body in the nerve cells (neurons) of the central nervous system and the peripheral nervous system.

Research – New Migraine drugs In The Pipeline (1)

So what is the function of CGRP? Of the many functions, CGRP is a powerful vasodilator and it contributes significantly in the transmission of pain message through the body. It is also believed to play a critical role in cardiovascular homeostasis as well as in processing noxious stimuli that has the potential to damage the tissues of the heart.

The development of drugs which are essentially CGRP receptor antagonist is in the pipeline aimed at helping migraineurs the world over cull the pain of their migraine episodes. How does the CGRP receptor antagonist do this? It has been observed that during the onset of a migraine attack, CGRP binds to CGRP receptors and activates these receptors which then transmit pain signals. CGRP receptor antagonist prevents the CGRP from binding on to CGRP receptors thus circumventing the transmission of pain signals causing migraine pain.

Telecagepant was such a CGRP receptor antagonist drug developed by Merck & Co. and was undergoing Phase III clinical trials but the trials were abandoned after identification of two patients with significant elevations in serum transaminases indicating liver damage. However, similar drugs without such side-effects are now being designed. CGRP receptor blockers also significantly reduce nausea and are more desirable in total benefit than triptans. As per Peter Goadsby, MD, PhD, director of UCSF’s Headache Center, “So this is a way for it to be effective and adds a safety bonus to the patients and it seems to be better tolerated.” (2)

There is another approach to drug design and development aimed at reducing the misery of migraineurs and it comes from the side of serotonin activity. In this class, one investigational drug of note is Lasmiditan thought of by Eli Lilly & Co and being designed to treat acute migraine by CoLucid Pharmaceuticals. These drugs are technically serotonin receptor agonists and selectively bind to the 5-HT1F receptor subtype. Unlike triptans these drugs do not constrict the heart vessels and have lesser side-effects. Trials have shown that administration of this drug reduced migraines to almost nothing within a two-hour period in almost 60% of the patients also tackling nausea and photophobia beautifully. The drug is expected to be ready by 2014. As per Dr. Goadsby, “Lasmiditan is now that finished its phase two studies and clearly works. It does not have the same sort of liver effects as its predecessors and will move on into phase three. That is again for acute migraine treatment. So it is a safe and totally different action than what we currently have.” (2)

 

SOURCES:

  1. Image by Ponsulak; Freedigitalphotos.net; March 2012; http://www.freedigitalphotos.net/images/view_photog.php?photogid=1983
  2. Cutting Edge Treatments For Migraines: More Than Just A Headache; Ivanhoe.com; March 2012; http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=29106&channelid=CHAN-100018

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Cambia Approved For Migraines In Canada

Health Canada has given a notice of compliance/approval to Stellar Pharmaceuticals’ generic drug Cambia. Cambia is used for the treatment of acute migraines in adults with or without aura. The chemical composition of this oral solution comprises of diclofenac potassium. Cambia is actually manufactured by Tribute Pharmaceuticals, a wholly owned subsidiary of Stellar Pharmaceuticals. (1)

Cambia (R) – Diclofenac Potassium Approved In Canada For Migraineurs(2)

This is a relief to the Canadian migraineurs as the generic drug is affordable. In Canada Cambia will be marketed exclusively by Nautilus Neurosciences. Oral tablets of diclofenac potassium have been available to the U.S patients since May 2010 after FDA approval. Diclofenac Potassium is a non-steroidal anti-inflammatory drug (NSAID) and a benzeneacetic acid derivative.

Cambia and other brands of diclofenac potassium are contraindicated for use in persons with cardiovascular condition, peri-operative pain in the setting of coronary artery bypass graft and those with gastrointestinal sensitivity and conditions.

According to Rob Harris, President and CEO of Stellar Pharmaceuticals, “We feel that CAMBIA(R) represents a logical first line prescription treatment choice for acute migraine, especially when over-the-counter medicines that offer some relief with milder forms of migraine pain fail, and where side effects or tolerability issues with the triptan class of drugs becomes a concern. With CAMBIA(R), Canadian physicians now have a new treatment option with comparable efficacy to the oral triptans but with a faster onset of action.”(3)

SOURCES:

  1. Nautilus Neurosciences, Inc. Announces a New Approval for CAMBIA® for the Acute Treatment of Migraine; Marketwatch -PR Newswire; March 2012; http://www.marketwatch.com/story/nautilus-neurosciences-inc-announces-a-new-approval-for-cambia-for-the-acute-treatment-of-migraine-2012-03-19
  2. Image by Stuart Miles; Freedigitialphotos.net; March 2012; http://www.freedigitalphotos.net/images/view_photog.php?photogid=2664
  3. Health Canada Approves CAMBIA(R) for the Treatment of Acute Migraine; Marketwatch – Marketwire- Press Release; March 2012; http://www.marketwatch.com/story/health-canada-approves-cambiar-for-the-treatment-of-acute-migraine-2012-03-16

 

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Co-morbidity of Migraine and Depression In Women

Most of us are aware that migraineurs have some comorbid conditions like generalised anxiety disorder, cardiovascular conditions and gastrointestinal disturbances. Research now has it that migraineurs especially women who have either experienced repeated episodes of migraines in the past or continue to have migraines are more likely to experience depression.

Women Migraineurs Very Likely To Develop Depression (1)

In fact another report goes on to suggest that the most ‘important’ comorbidity of migraines is depression with as many as 40% of all migraineurs also suffer from forms of depression. (2)

New research released on 23rd of February which was presented at the American Academy of Neurology’s 64th Annual Meeting showed that migraining women specifically had a higher risk of almost double for developing depression than those women who did not experience migraines.

This study had examined the medical history of 36,154 women participants. The whole population studied were classified into 4 groups:

  • Women with migraines and experiencing aura
  • Women with migraines who do not experience aura
  • Women who had suffered migraines in the past but have not in the last one year
  • Women who never had migraines

It was observed after collection and analysis of data that as many as 18% of the studied population had either current or past history of migraines and that of this group of 6, 456 women almost half of them developed depression 14 years on.

Another observation of note was that the results in terms of the probability of developing depression for women migraineurs remains almost same regardless of the type of migraines they experience (i.e. with or without visual aura)

The results did not vary substantially, regardless of the type of migraine. Those with aura, which is described as visual disturbances that appear as flashing lights, zigzag lines or a temporary loss of vision, had the same risks as other types of migraine.

According to Tobias Kurth, MD, ScD, with Brigham and Women’s Hospital in Boston and Inserm in France and a Fellow of the American Academy of Neurology, “This is one of the first large studies to examine the association between migraine and the development of depression over time. We hope our findings will encourage doctors to speak to their migraine patients about the risk of depression and potential ways to prevent depression.” (3)

This is a cue to doctors and headache specialists who treat migraineurs for assessing the patient for possible symptoms of depression and chalking out an appropriate management program for them.

SOURCES:

  1. Image by David Castillo Dominici; Freedigitalphotos.net; February 2012; http://www.freedigitalphotos.net/images/view_photog.php?photogid=3062
  2. Comorbidities of Migraine – Page 4; Lisa K Mannix, MD; February 2012; http://www.headaches.org/pdf/CME_Mono02.pdf
  3. Migraine Increases Risk Of Depression In Women; Medical News Today; February 2012; http://www.medicalnewstoday.com/articles/242091.php

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