Table of Contents
Introduction
Migraine is a common brain condition, and many people have it. Because the cause is not known precisely, different therapeutic approaches have been tried over many years.
But here’s something cool! There is a new way to fight migraines called CGRP receptor antagonists or Gepants. These medicines are like blockers and stop CGRP from causing migraines. So, what exactly is this CGRP? How does it cause migraine? And how can it be blocked? Keep reading to find out.
What Is CGRP?
CGRP (calcitonin gene-related peptide) is a special type of protein that helps control different functions in the body. It is found in the body’s nervous system and is primarily released from sensory nerves (which carry information about body sensations like smell, taste, touch, etc.). Thus, CGRP plays a big role in the pain pathways of migraines by causing inflammation, enlarging the blood vessels in the brain, and bringing in the pain signals.
CGRP is distributed both in the central and peripheral nervous systems. These are expressed mainly in C and A-delta nerve fibers. There are three types of CGRP receptors. The CGRP-1 is a G protein-coupled receptor. This is also known as the calcitonin-like receptor. The second class of receptors is known as RAMP1. These receptors help in the formation of functional CGRP receptors. Another important CGRP receptor is the RCP receptor, which is important for G-protein signaling. However, CGRP receptors also play an important role in the pathogenesis of migraine.
How Does CGRP Play a Role in Causing Migraines?
Here’s how this tiny CGRP causes migraines when in excess.
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CGRP activates a group of neurons originating in the trigeminal ganglion, which provides sensation to the face and head and is responsible for migraine attacks. This system is called the trigeminovascular system.
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CGRP causes the blood vessels in the brain to expand, causing migraine pain.
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CGRP causes the body to release tiny inflammatory mediators, especially in the nervous system. This makes the peripheral and central nervous systems more sensitive, which means more pain signals.
What Are CGRP Inhibitors?
CGRP inhibitors are used to treat migraines by blocking the CGRP protein from binding to its receptors. This reduces brain inflammation and migraine pain.
They are split into two groups:
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Monoclonal Antibodies: These are very large molecules that can block the CGRP protein or its receptors. They are available in injectable forms, either subcutaneous or intravenous, and are given monthly or four times a year.
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CGRP Receptor Antagonists (Gepants): These are small molecules that block CGRP receptors and prevent CGRP binding. They are provided in pill form. They can be taken as needed or on a regular basis. Zavegepant, which belongs to this group, stands out because it is the only one available as a nasal spray! This can give you quick relief because it gets right into the action.
A Note on Specific CGRP Inhibitors Drugs:
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Olcegepant: This is the first CGRP receptor antagonist. It is a selective antagonist that works mainly on RAMP1 and is administered intravenously. This drug directly competes with the CGRP molecule and prevents physiological and cellular changes caused by CGRP. However, according to some researchers, the ability of this drug to constrict the blood vessels is very minimal.
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Telcagepant: This is also a selective CGRP receptor antagonist, which is given orally. This drug also acts on RAMP1 receptors. A 300-milligram dose of this drug is useful to provide migraine pain relief for 24 hours. This drug dose does not cause a significant amount of vasoconstriction.
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Ubrogepant: This is an orally administered small molecule antagonist of the CGRP receptor. Though the drug is still in the clinical trial phase, it has shown relief from acute pain for 48 hours. Nausea, dry mouth, and tiredness are the potential side effects of this drug. The maximum dose for 24 hours is 200 milligrams.
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Rimegepant: This drug got approval from the FDA in 2020. It is known for blocking the action of the CGRP-1 receptor. It is useful in treating conditions like migraine with or without aura. The maximum dose for 24 hours is 75 milligrams.
Uses of CGRP Inhibitors
Let’s find out their uses.
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CGRP inhibitors can reduce the frequency and severity of migraines and the pain associated with them. Therefore, they are used as preventive medications. Monoclonal antibodies and Gepants are used for this.
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CGRP inhibitors can get right into action and stop them quickly, so they are used in acute migraine treatment. Rimegepant and Ubrogepant are the approved pills for acute treatment. Another one, Zavegepant, an intranasal CGRP antagonist, is also used in acute treatments.
What Are the Side Effects of CGRP Inhibitors?
Common side effects are dry mouth, gastrointestinal problems like constipation, diarrhea, vomiting, injection site reactions, and urinary tract infections. It can cause joint and back pain. There are some rare side effects, too, like hypertension, hair loss, anaphylaxis (an allergic reaction that is severe), liver toxicity, and erectile dysfunction.
Who Should Consider CGRP Inhibitors?
You may try CGRP inhibitors if:
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You get a lot of migraines.
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Regular medications are not helping.
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You have side effects from other medicines.
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You have chronic migraines.
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You have migraine with aura.
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You have bad headaches from taking too many medicines.
Pregnant women are not supposed to take these meds. However, there is limited data. And for individuals with cardiovascular issues, CGRP inhibitors are usually safe and don’t make heart issues worse.
Conclusion
Migraine is associated with neurovascular changes in the brain. One of the most common chemicals associated with this is CGRP, which is associated with the dilation of blood vessels. CGRP antagonists are a new generation of drugs that prevent the action of the molecules. These drugs act on the receptor site of the molecule and prevent its functioning.
Key Takeaway From iCliniq
CGRP are chemical messengers that play a big role in causing migraines. Scientists have made special medicines called CGRP inhibitors that can target and block them. If you are tired of dealing with migraines, don't worry or take the stress! iCliniq doctors can help you manage them well with the right medicines.
