Nonsteroidal anti-inflammatory drugs for migraine

Nomigren

A combined drug for relieving headache attacks of vascular origin, it helps people with migraine well. Nomigren is a relatively safe drug that contains propyphenazone, caffeine, ergotamine, meclosamine and kamilofin. "Nomigren" relieves headaches not only of a migraine nature - it is an antispasmodic and analgesic. When taking Nomigren for the first time, choose the minimum dosage, since the list of contraindications and side effects of the drug, despite its relative safety, is large.

Nomigren

Bosnalek, Bosnia and Herzegovina

acute attacks of migraine (including those accompanied by an aura);
migraine-like headaches of vascular origin. from 127

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Modern medicines

A special project about modern medicines, the history of their creation, development methods and development trends.

The special project partner, Cytiva, was formed as a result of the sale of the GE Healthcare Biopharma division to Danaher Corporation. Cytiva is a global provider of technologies and services that advance and accelerate the development and manufacturing of therapeutics. The company has a rich heritage dating back hundreds of years. Cytiva's clients conduct life-saving activities ranging from basic biological research to the development of innovative vaccines, biologics and novel cell and gene therapies. The company's mission is to provide the tools and services they need to do things better, faster and safer, leading to better outcomes for patients.

The first two articles of our special project “Modern Medicines” were devoted to general issues of how the drug industry developed [1] and how scientists search for new drug targets [2]. This article opens a number of news materials about interesting modern medicines.

Migrepam

The main active ingredient of Migrepam is zolmitriptan. This anti-migraine drug targets exactly the cause of the headache, so it helps to cope with even long-term migraines and severe episodes of headaches. In addition to headaches, Migrepam also relieves symptoms such as fear of light and sensitivity to sounds, nausea and sweating. Improvement occurs approximately an hour after taking the tablet. But not everyone can use this drug due to side effects. Therefore, be sure to consult your doctor before purchasing Migrepam.

Migrepam

Migrepam® effectively relieves headaches and other symptoms of migraine (nausea, photophobia, phonophobia).
Equally effective against migraine with aura, without aura and migraine associated with menstruation. from 166

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Clinical manifestations

The symptoms of the disease are difficult to describe; patients cannot convey in words all the sequential sensations that arise. Anyone who has not experienced the manifestations of migraine will not be able to fully understand the clinical picture of the disease.

The description of the pathological process includes the following features:

1. The attack begins with painful sensations on the right or left side of the head. Initially, the discomfort affects the temporal lobe, but can move to the eye or back of the head.
2. Pain can vary in severity, from mild to severe. Some patients report pulsating shocks, others mention sharp, dagger-like impacts.
3. The appearance of attacks of nausea and muscle discomfort are considered standard symptoms.
4. Men may experience involuntary lacrimation, rhinitis, and a rush of blood to a certain part of the body.

A standard attack lasts from 4 hours to one day. It occurs in the evening or night hours, before the onset the patient experiences irritability, weakness, loss of appetite or complete refusal to eat.

In some patients, a standard migraine is accompanied by an aura - visual changes. They see spots, crooked lines before their eyes; optical illusion is combined with loss of sensitivity in one of the parts of the body: lower or upper limb, half of the face. The aura occurs for 10-60 minutes and is a harbinger of an imminent attack.

Sumamigren

This drug contains the substance sumatriptan, which has serotin-generating and anti-migraine effects. The headache is relieved quickly because vasoconstriction occurs selectively. Sumatriptan is a truly effective substance that helps quickly get rid of a migraine attack. “Sumamigren” contains only 50 mg of sumatriptan, so during an intense migraine attack you can take two tablets at once. Moreover, the headache will go away in about 15-20 minutes. But Sumamigren has serious contraindications and side effects, so it must be prescribed by a doctor.

Sumamigren

Polfa, Poland

Relief of migraine attacks with or without aura.
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Primary sources of migraine

Medical studies have not revealed the exact prerequisites for the occurrence of the disease in representatives of both sexes. Genetic predisposition plays a major role in its formation, and individual associated factors play a secondary role.

The occurrence of wave-like attacks of cephalalgia is caused by weather conditions and concomitant pathologies, represented by:

• depressive syndrome, apathy;
• bipolar disorder;
• unreasonable anxiety, worry;
• severe stress or post-traumatic stress conditions.

Exacerbation of the disease is associated with one or more factors:

• stress, tension;
• fasting, improperly selected dietary nutrition;
• excessive fatigue, insufficient sleep;
• strong odors or tobacco smoke;
• changes in weather conditions, including sudden increases in temperature and humidity;
• quality characteristics of indoor air;
• too bright and dim lighting, etc.

The strength and significance of these triggers is not fully understood.

Amigrenin

The active ingredient of Amigrenin is also sumatriptan, but in a higher dosage than the previous medicine. Amigrenin quickly relieves migraine symptoms, not only headaches, but also other symptoms. Moreover, if you take a pill at the beginning of the aura, you can even avoid a headache. The drug contains a high dosage of sumatriptan - 100 mg - which is why Amigrenin has such a large list of contraindications.

Amigrenin

Veropharm / Lance-Farm, Russia

The active substance of the drug Amigrenin interacts with type I 5-hydroxytryptamine receptors located in the smooth muscles of the walls of blood vessels in the brain, selectively constricts blood vessels in the carotid artery system, and inhibits the activity of the trigeminal nerve.
All this helps reduce the severity of migraine pain. The clinical effect is observed after 30 minutes. from 187

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Targeted therapy for migraine: a solution to the problem?

Since migraine is a chronic disease and the effectiveness and safety of the drugs used for prevention is poor, there is clearly an unmet need in this area; however, there are few new drugs specifically developed for this indication [14].

Amgen and Novartis can boast of a breakthrough today, having received approval in May 2021 for the use of the targeted drug Aimovig erenumab antibodies ) for the prevention of migraine in adult patients [20]. This is the first fully human antibody to be commercialized whose preventive effect is due to binding and blocking the CGRP receptor, which is considered critically important in the development of migraine (Fig. 3).

Figure 3. Aimovig specifically binds to the CGRP receptor, preventing CGRP from binding to it. The binding of CGRP to its receptor in a molecular complex (shown on the left) results in the transmission of pain signals associated with migraine. In people with migraine, CGRP levels are elevated during a painful attack and return to normal levels when the migraine pain subsides.

About Aimovig® (erenumab) in migraine prevention

Aimovig was approved after three series of clinical trials, the results of which, although slightly different, were similar in one thing: the drug showed a significant reduction in the number of days with attacks and the total duration of migraine pain. Moreover, in phase III trials, in 50% of patients taking 140 mg of Aimovig, the number of painful days decreased by half compared to placebo, and the safety and tolerability of the drug turned out to be quite similar to placebo [21], [22]. . These results are very encouraging, and it is clear that although Aimovig is not a panacea, its use will definitely change the lives of patients suffering from frequent and severe migraines for the better.

Antibody purification using continuous countercurrent chromatography

Biotechnologically derived antibodies can be purified using the chromatography equipment of this material's partner, Cytiva. This is done in continuous counter-current chromatography (PCC) mode on an ÄKTA pcc . In combination with the minimal dimensions of the system, continuous chromatography technology ensures the most efficient use of the chromatographic sorbent (resin). This method is particularly suitable for the purification of unstable molecules, as the rapid process ensures the stability of the target product. The ÄKTA pcc system is based on the well-established and widely used ÄKTA chromatography system platform by scientists around the world. Key features of the ÄKTA pcc system:

• Flow rate: 0.5–75 ml/min.
• Maximum operating pressure: 20 bar.
• Supports three and four column PCC configuration (3C and 4C PCC).
• Integrated UV detectors: one tunable wavelength (three values) and three fixed wavelength (280 nm).
• Monitors for tracking pH and conductivity readings.
• Interactive visualization that continuously shows column status and process progress.
• Trend lines that allow you to immediately begin analyzing the information received about the process.

ÄKTA chromatography systems can be used in conjunction with AxiChrom columns, although they are also suitable for larger scale protein purifications. A wide range of column sizes of the same type (Figure 4) allows protein purification to be scaled up with minimal parameter changes.

Figure 4. AxiChrom is a family of pilot-scale to industrial-scale protein purification columns with i.d. diameters of 50–1600 mm. AxiChrom columns successfully combine standardization and customization and are compatible with a variety of advanced media, such as MabSelect SuRe™ antibody purification resin.

Cytiva's research has confirmed the similarity between the protein purified in the laboratory and in production. In this case, the volume of the drug was scaled by 294 times (Fig. 5).

Figure 5. Comparison of chromatograms obtained using ÄKTA pcc on HiTrap columns (a) and AxiChrom 50 columns (b)

Material provided by our partner - Cytiva

Sumatriptan

This drug is one of the best in the fight against persistent migraine. The active ingredient of the drug is sumatriptan succinate. "Sumatriptan" selectively constricts blood vessels without affecting cerebral blood flow. The drug not only relieves headaches, but also helps relieve other symptoms of migraine: sensitivity to light and noise, nausea. The migraine subsides just 15 minutes after taking the pill. Sumatriptan is a drug with a stable effect, so migraine attacks do not return for a long time after taking it.

Sumatriptan

Migraine - symptoms and treatment

Getting rid of migraine pain is a complex, complex task that requires not only drug therapy, but also lifestyle adjustments and non-drug treatment.

Migraine treatment includes:

1. Lifestyle correction, informing the patient about the nature of the disease, behavioral therapy.
2. Treatment of attacks - aimed at relieving a separate migraine attack, can be used in a single variant if attacks are rare.
3. Preventive treatment - prescribed at the request of the patient or when attacks become more frequent and their severity increases.

How to get rid of migraine pain

As a rule, a patient with migraine begins to take simple or combined analgesics or NSAIDs on his own before contacting a neurologist. In this case, it is necessary to adhere to therapeutic doses of drugs, avoid drugs containing caffeine and codeine, due to the high risk of developing dependence with withdrawal symptoms. Abuse of such drugs can cause chronic daily headaches, which will significantly complicate further treatment.

Medicines for the treatment of migraine attacks

Specialized drugs for the treatment of migraines are triptans . They bind to serotonin receptors and activate them. This suppresses the release of the key neurotransmitter CGRP, which is associated with the development of migraine. This mechanism blocks the main pathological link in the development of migraine. Taking triptans selectively constricts the vessels of the dura mater, reduces the permeability of the vascular wall and reduces inflammation and pain, as well as the intensity of the accompanying symptoms of migraine.

There are several types of triptans; the selection of the drug is carried out by a neurologist individually.

Basic principles of taking triptans:

• The doctor should teach the patient to distinguish between different types of headaches and to identify migraines.
• The sooner a patient takes the drug, the more likely it is to work. Medicine taken in the first minutes of an attack is effective in about 80% of cases. A triptan taken two hours after the onset of an attack is effective in 20% of cases.
• During a migraine attack, the gastrointestinal tract is paralyzed, causing the drugs to be poorly absorbed. Therefore, they are recommended to be taken together with prokinetics - drugs that improve the motility of the stomach, duodenum, and in some cases, the small and even large intestine.
• The lack of effect after the first dose of the drug does not indicate its ineffectiveness. It is necessary to take the drug for three more attacks.

What other medications help treat migraines?

At the request of the patient or in the event of an increase in the frequency of attacks and an increase in their severity, preventive treatment may be prescribed.

Medicines to prevent migraine attacks

At the end of September 2021, the FDA (Food and Drug Administration) approved a new drug for the treatment of migraines - Qulipta (Atogepant). It targets the neuropeptide CGRP, which is elevated in migraine and is considered a major biomarker of the disease [39].

Non-drug treatments for migraines

Non-drug treatment methods include biofeedback (BFB), a computer-based method of self-regulation, as well as transcranial electrical stimulation methods, hyperbaric oxygenation and other options for individually selected physical therapy. The effectiveness of these methods has not been sufficiently studied and is questioned.

Is it worth using folk remedies to treat migraines?

According to the WHO definition, “Traditional medicine is the sum total of the accumulated knowledge, beliefs and skills, based on the theories, beliefs and experiences of indigenous peoples and peoples of different cultures, whether we can explain them or not, that are used to maintain health and also for the prevention, diagnosis and improvement of physical and mental disorders” [25].

When it comes to faith and traditions, it is difficult to talk about their scientific evidence. Herbal medicine is closest to the concept of traditional medicine - treatment using herbal remedies that contain medicinal substances. However, large and well-controlled studies have not been conducted to prove the effectiveness of herbal medicine.

There are some pilot studies showing the effectiveness of some herbal remedies:

• Oil of lavender, peppermint, basil, anise. Shown to be effective in reducing migraine attacks [34][35][36].
• Butterbur (Petasites hybridus). Can reduce the frequency and severity of migraine attacks [27].
• Hemp and mushrooms of the genus Psilocybe. Shown to be effective for migraine [28][29]. However, their use is contrary to the legislation of the Russian Federation.
• Willow bark extract. Contains an anesthetic substance - acetylsalicylic acid, so it can be effective for migraines.
• Ginger. Ginger powder has been shown to be effective and well tolerated for migraine [30].
• Caffeine in coffee, tea, mate. Shown to be effective in combination with paracetamol and sumatriptan [31].
• Coriander. Coriander syrup has been shown to be effective in reducing the duration and frequency of migraine attacks and reducing pain [32].
• Dong cai root (Angelica sinensis). Can relieve migraine symptoms [33].
• Valerian. There is no evidence that valerian objectively helps with migraines. However, thanks to its calming and hypnotic effect, a positive effect is possible during migraine attacks.
• Pyrethrum (Tanacetum parthenium). There is insufficient data to demonstrate efficacy compared with placebo [26].
• Rosemary, linden, raw potato cuttings, honeysuckle, horseradish, mullein, yarrow, teaberry, dried cherries, alecost, bananas, spinach, salmon protein, watermelon, common hops, betoni, evodia. Evidence of effectiveness is insufficient.

The use of folk remedies for migraine should be viewed critically. The reason for this is the lack of evidence and contradictory data, as well as the fact that most of the studies were conducted in countries where the requirements for clinical trials are lower than in the USA and EU countries.

You should be especially careful with the use of herbal medicine in case of moderate to severe attacks and complicated migraine.

How to treat migraine during pregnancy

Features of migraine treatment in pregnant women:

1. A full examination is carried out to exclude the secondary nature of the disease.
2. Preference is given to non-drug methods:
3. behavioral recommendations - adjusting work and rest schedules, avoiding stress, keeping a headache diary to identify and exclude migraine triggers;
4. methods are used that are not used so often in the treatment of migraine in non-pregnant women due to the lack of evidence of their effectiveness: psychotherapy, biofeedback [37], physiotherapy methods - transcranial electrical stimulation, hyperbaric oxygenation (pressure chamber), acupuncture, osteopathy, massage.

Basic principles of drug treatment during pregnancy:

• Independent, uncontrolled use of medications without consulting a doctor is unacceptable.
• Any prescription must be justified; the benefit must outweigh the potential risk.
• Preference is given to therapy with one drug - the most researched and safe, to quickly stop the attack, in the minimum effective dose. The dose may exceed the average therapeutic dose, taking into account the metabolic characteristics of a pregnant woman.
• Prophylactic treatment should be avoided due to its duration and contraindications to most medications. However, prophylactic use is possible if there are several indications for prescribing one drug, for example, the use of beta-blockers for arrhythmia, arterial hypertension and migraine simultaneously.
• It is recommended to avoid prescribing any medications in the first trimester and two weeks before the expected birth.
• When taking medications, strict monitoring and timely diagnosis of the condition of the pregnant woman and fetus are necessary.

For ethical reasons, direct studies have not been conducted on pregnant women, so at the moment there is no drug for the treatment of migraines whose safety has been fully proven. Sumatriptan is the most researched and safest of the triptans used during pregnancy. Admission is possible if the benefit outweighs the possible risk [37]. For mild migraine attacks, paracetamol is used, for more serious ones, ibuprofen is used in the first two semesters; metoclopramide can be prescribed to enhance the effect. The use of these drugs during pregnancy is not considered completely safe; they are taken under medical supervision with caution and in a minimal dosage.

Migrainous status

In this case, headaches have the nature of painful attacks, are accompanied by neurological symptoms, and last for several days.
Another option for the development of the disease is a migraine attack that lasts for three days and does not go away after taking medications. In this case, headaches are accompanied by:

• vomiting;
• signs of dehydration;
• decreased vision or loss of visual fields;
• apathy;
• convulsive seizures are possible;
• fainting.

Literature

1. Three generations of drugs;
2. Search for drug targets;
3. Sanoeva M.Zh. and Saidvaliev F.S. (2016). Migraine - yesterday, today, tomorrow. A modern view of the problem. "International Neurological Journal". 8, 72–78;
4. How a migraine happens. Johns Hopkins Medicine;
5. Migraine headaches. (2018). WebMD;
6. Paul L. Durham. (2006). Calcitonin Gene-Related Peptide (CGRP) and Migraine. Headache
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   46 , S3-S8;
7. What to know about the new anti CGRP migraine treatment options. (2018). American Migraine Foundation;
8. Silberstein S. D. (2016). Migraine. MSD Directory;
9. Migraine triggers: your personal checklist. (2019). WebMD;
10. Rusakova E. (2018). The FDA has approved the drug to prevent migraines. N+1;
11. Kolata G. (2018). The FDA approves the first drug designed to prevent migraines. The New York Times;
12. Theo Vos, Amanuel Alemu Abajobir, Kalkidan Hassen Abate, Cristiana Abbafati, Kaja M Abbas, et. al.. (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet
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    390 , 1211-1259;
13. Francesca Puledda, Kevin Shields. (2018). Non-Pharmacological Approaches for Migraine. Neurotherapeutics
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    15 , 336-345;
14. Doodipala Samba Reddy. (2013). The pathophysiological and pharmacological basis of current drug treatment of migraine headache. Expert Review of Clinical Pharmacology
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    6 , 271-288;
15. Ogbru A. and Ogbru O. Prescription migraine medications. RxList;
16. Boyce S., Ali Z., Hill R. G. (2001). New developments in analgesia. Drug Discovery World;
17. Azimova Yu.E. (2017). Triptans: an era of specific treatment for migraine. "Nervous diseases". 1, 10–14;
18. Ameri M. and Lewis H. (2018). The evolution of transdermal drug delivery and treating migraine. Drug Discovery World;
19. Migraine medications. (2013). TMedWeb;
20. Dmitriev R. (2019). "Aimovig" will turn chronic migraine into episodic. "Mosmedpreparaty";
21. Aimovig (erenumab) for the treatment of episodic migraine. Clinical Trials Arena;
22. Khoruzhaya A. (2018). A new anti-migraine drug goes on sale. "Neuronews";
23. Targeted therapy is a targeted strike against the disease.

A child has a migraine attack: what to do?

When an attack occurs, the child must be placed in a horizontal position. It is better to darken the windows in the room, turn off light and sound sources, and also provide fresh air. In case of severe nausea, it is advisable to relieve the condition by inducing vomiting. During an attack, sweet tea and sleep will be helpful.

In addition to undergoing a course of osteopathic treatment for childhood migraines, parents should follow several simple recommendations that will help reduce the risk of developing new attacks in their child:

• do not limit the child’s contacts with peers and other people;
• Explain to the child what the disease is;
• maintain a daily routine;
• exclude (or reduce to a minimum) foods such as salty foods, preservatives, chocolate, citrus fruits, nuts from the child’s diet;
• avoid excessive loads;
• limit the child’s presence near the computer;
• replace medications that can cause an attack;
• use personal hygiene products without fragrances;
• If a child has bad habits, try to rid him of them.

Causes of headaches in children

The prerequisites for the development of migraine are the following provoking factors:

• excessive or insufficient sleep;
• changes in barometric pressure and weather;
• psychological and physical fatigue;
• overstrain of the visual organs from watching TV or from prolonged work at the computer;
• negative emotions;
• consumption of foods with excessive amounts of tyramine (sweets, nuts, citrus fruits, chocolate, cheese, smoked meats, eggs);
• hereditary predisposition;
• heat and stuffiness;
• certain medications;
• some odors;
• driving;
• bad habits.