CGRP Receptor Antagonists to Treat Migraines
Migraine headaches are a type of headache characterized by recurrent episodes of moderate to severe throbbing or pulsating pain. These headaches can last anywhere from four to 72 hours if left untreated.
CGRP antagonists are a type of medication used to treat migraine headaches. CGRP stands for calcitonin gene-related peptide, which is a neuropeptide (protein in the brain). CGRP plays a role in the development of migraines by causing inflammation and pain in the trigeminal nerve and causing blood vessels in the brain to dilate (widen).
These medications have been found to be effective in relieving migraine symptoms and preventing future attacks. They can help reduce the frequency and intensity of migraines, as well as improve overall quality of life for migraine sufferers.
Calcitonin gene-related peptide (CGRP) is released in the trigeminovascular system, a network of nerves and blood vessels on the brain’s surface. The release of CGRP and attachment to nerve receptors in this network causes vasodilation (expansion or widening) of blood vessels in the brain, increases neuronal excitability, and activates neurogenic inflammation. This cascade of events may lead to a migraine with its characteristic throbbing, pulsating headache and pain.
CGRP antagonists target the underlying cause of migraines. By blocking CGRP from attaching to the nerve receptor, these medications can help reduce neurogenic inflammation and pain sensitization, which are important factors in migraines.
There are two types of calcitonin gene-related peptide (CGRP) antagonists: CGRP monoclonal antibodies (mAbs) and CGRP receptor antagonists (or blockers).
- CGRP monoclonal antibodies: These bind to the CGRP protein or to the CGRP receptor. Binding to the CGRP protein changes the structure or shape of CGRP so it cannot “fit” into the nerve receptor. Other CGRP mAb may bind to the nerve receptor to block CGRP from attaching. Through this mechanism, CGRP mAbs have been found to be effective in preventing migraines. CGRP mAbs can be administered through injection into the fat layer under the skin (subcutaneous) or infusion into a blood vein. CGRP mAbs are administered either monthly or every 3 months, depending on the specific medication.
- CGRP receptor antagonists (blockers): These bind to the CGRP receptor on nerve tissue. This blocks CGRP from attaching to the receptor, thereby preventing CGRP’s actions. This type of CGRP antagonist is also called the “gepants”. Some gepants are used to treat a migraine and some are used to prevent migraines.
Overall, CGRP antagonists work by targeting CGRP to reduce inflammation in the brain and prevent migraine pain and, depending on the specific CGRP antagonist, may be used as acute or preventive treatment of migraine.
It is important for people with migraines to consult with a healthcare professional who can provide treatment guidance based on individual factors.
Directions for taking calcitonin gene-related peptide (CGRP) antagonists are based on the specific medication. When it comes to using or taking CGRP antagonists, here are some important points to keep in mind:
- Administration: Directions for taking CGRP antagonists are based on the specific medication.
- CGRP mAb for subcutaneous injection: These may come as prefilled (pre-measured dose) syringes, pens or autoinjectors for one-time use. A healthcare professional will provide training on proper use, including how to select an injection site and use the specific CGRP mAb administration device. It is important to read the medication-specific instructions.
- CGRP mAb for intravenous infection: This CGRP is administered in the doctor’s office or clinic.
- CGRP gepant for acute treatment: The gepant tablet or inhaler should be used as early as possible at the start of a migraine. It is important to follow the instructions on the prescription label and read the medication-specific instructions for swallowing or dissolving a tablet, or for using the nasal inhaler.
- CGRP gepant for prevention: The gepant tablet should be taken on a routine basis (daily or every other day, at about the same time of day). Follow the instructions on the prescription label and read the medications-specific instructions.
- Dosage: The dosage of CGRP antagonists will vary depending on the specific medication and the individual's condition. Your doctor will determine the appropriate dosage for you.
- Precautions: It's important to be aware of certain precautions when using CGRP antagonists. For example, these medications may decrease the reflex vasodilatory response, which could potentially worsen conditions like Raynaud phenomenon (RP). Additionally, there have been concerns about the potential risk of stroke or heart attack in individuals at risk for these conditions.
- Side effects: Like any medication, CGRP antagonists may have potential side effects. Common side effects may include pain at the injection site and changes in blood pressure. However, it's important to note that there is limited safety information available regarding the long-term effects of CGRP antagonists.
- Pregnancy: There is currently limited information regarding use of CGRP antagonists in pregnancy. It is important to consult with a healthcare professional for guidance based upon individual-specific factors.
Remember, this information is not a substitute for medical advice. Always consult with your doctor or healthcare provider before starting or changing any medications.