Prevention Of Migraine Headaches Research Articles

Study protocol for LOMCAD Trial: Effect of lomerizine hydrochloride to prevent recurrence of cerebral ischemic events in CADASIL patients

ObjectivesCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride. Materials and MethodsThis is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects. ConclusionWe have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients. RegistrationThe LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

Development of a Stability-Indicating Purity Method for Ubrogepant Through Stress Degradation Analysis, Extraction, and Characterization of Unidentified Degradation Products Using Flash Chromatography, NMR, IR, and LC–MS

Abstract Background Ubrogepant is a prescription medication used to prevent migraine headaches. It is currently available in tablet form. Objective The goal of this work is to investigate the drug degradation profile of ubrogepant, as well as to isolate and characterize undiscovered ubrogepant degradation products by utilizing LC–MS, NMR, and IR spectroscopic analytical techniques and, furthermore, to develop a high-resolution, sensitive, stability-indicating analytical approach for detecting and quantifying ubrogepant degradation products in its pharmaceutical formulation. Methods To identify and quantify the degradation products of ubrogepant in pharmaceutical products, a novel gradient reverse-phase HPLC (RP-HPLC) technique with a photo diode array (PDA) detector was developed by utilizing a C18 stationary phase column. The eluent comprised a mixture of acetonitrile and water with 0.1% (v/v) ortho-phosphoric acid. To establish the intrinsic stability of the ubrogepant pharmaceutical product, it was stress-tested under various degradation conditions, including water, alkaline, acid hydrolysis, photolytic, oxidative, and thermal. Flash chromatography was used to isolate the two major degradants, and the structures were determined using NMR (1H, 13C, distortionless enhancement by polarisation transfer-DEPT-135), IR, and LC–MS methods. Results The ubrogepant medication was relatively more degradable in alkaline and acidic conditions, and two unique degradation products were discovered. Based on spectroscopic and chromatographic evidence, it was conclusively demonstrated that these unique compounds were ubrogepant hydrolysis products. All degradation products were separated with a resolution greater than 2.0. The peak purity data showed that the ubrogepant peak in all of the stress samples examined was pure. Under all stress environments, ubrogepant achieved a minimum mass balance of 95%. The validated approach developed was sensitive enough to quantify ubrogepant degradation products at 0.03% of the ubrogepant test concentration. Conclusion The proposed method was found to be stability-indicating since it fits all of the regulatory authorities' typical requirements. This method is highly efficient for detecting and quantifying impurities in ubrogepant drug substances and drug products in QC laboratories. Highlights Two new degradation products of ubrogepant were successfully extracted and characterized using NMR, IR, and LC–MS spectroscopic methods. The proposed HPLC method can accurately quantify the degradation products of ubrogepant in pharmaceutical products and is sensitive enough to detect degradation products of ubrogepant as low as 0.17 µg/mL.

Аctual aspects of migraines preventive pharmacotherapy

Headaches are one of the most common causes of disability worldwide, with migraines coming to the fore. A new and promising preventive strategy to combat migraine is drugs from the group of monoclonal antibodies to calcitonin-a gene-related peptide. High efficacy, good tolerability, and the ability to increase patient compliance increase the interest of specialists in these drugs. A potentially significant reduction in the economic burden on society and healthcare also plays an important role as a significant impact on improving the quality of life of patients. Despite the prospects of using these drugs for the prevention of migraine headaches, not all aspects related to this have been fully considered and resolved to date.

Effects of nonprescription therapies on vestibular migraine: a questionnaire-based observational study.

Vestibular migraine (VM) is a common cause of recurrent vertigo. Migraine headache preventative therapies are currently prescribed to control vertigo symptoms in VM. Clinical trials of nutraceuticals for migraine headache prevention have shown positive outcomes, but, to date, there have been no studies to assess their effectiveness in the management of VM. To report the effects of nonprescription therapy management on VM symptoms. We undertook a prospective, questionnaire-based assessment of patients diagnosed with VM between November 2019 and August 2021 at two Sydney tertiary referral clinics. Patients were advised on optimising sleep, hydration, exercise and nutrition and instructed to use an over-the-counter combination product containing riboflavin 200 mg, magnesium 150 mg, coenzyme Q10 75 mg and feverfew 200 mcg. Symptom severity and frequency were assessed using the Dizziness Handicap Inventory (DHI), the Vertigo Symptom Score short-form (VSS-sf) and two visual analogue scales for severity (VAS-s) and frequency (VAS-f) before and 3 months after commencing treatment. In 82 participants (78% female;mean age, 44 ± 14 years) we recorded a decrease in DHI (mean, 16.8 [95% confidence interval (CI), 12.8-20.9], VSS-sf (9.3, 7.1-11.5), VAS-s (3.0, 2.2-3.8) and VAS-f (2.8, 2.1-3.4), equating to an improvement of 44.1%, 44.9%, 44.1% and 38.9% for each measure respectively. On the DHI and VSS-sf, 41 (50%) and 44 (53.7%) patients showed improvement in their symptoms; 39 (47.6%) and 36 (43.9%) patients noted no change and two patients reported worsening. The supplement was well-tolerated. The results provide preliminary evidence that VM symptom frequency and severity can be reduced by using nonprescription therapies.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report

BackgroundValproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms.Case presentationA 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation.ConclusionsClinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Comparing Prophylactic Effect of Levetiracetam, Sodium Valproate, and Propranolol in Pediatric Migraine: A Randomized Clinical Trial.

Epidemiologic studies point to an increased prevalence of migraine in children in recent decades. Migraine treatment involves acute and prophylactic therapy. Recently, such anti-epileptic drugs as Levetiracetam have been used to treat adult migraines. The present study aimed to compare the efficacy of Levetiracetam, Sodium Valproate, and Propranolol in preventing migraine headaches in children. In this clinical trial, children with migraine were randomly divided into three groups. Each group consisted of 13 children. Two groups were treated with Propranolol and Sodium Valproate, respectively. Another group (the case) was treated with Levetiracetam. The patients were assessed based on headache score, PedMIDAS, and headache frequency before and three months after the intervention. Finally, the data was analyzed using descriptive and analytical statistical methods. Levetiracetam significantly reduced the headache severity (P=0.026), frequency (P=0.024), and PedMIDAS score (P=0.001) in children with migraine. However, no significant difference was found between the three groups. The percentage of patients who experienced pain relief was detected as 69.24%, 92.31%, and 30.76% in the Propranolol, Sodium Valproate, and Levetiracetam groups, respectively. This study concluded that Levetiracetam can be used as a migraine prophylaxis drug in children.

Topiramate-Induced Oral Lichenoid Lesions: A Case Report

Topiramate is being widely used to prevent migraine headaches and treat epilepsy and mental disorders; however, Oral Lichenoid Lesion (OLL) is one of its rare side effects. The present report has been provided based on a patient case study who had developed OLLs following treatment with topiramate. The patient was a 50-year-old woman referred to a psychiatric clinic with complaints of severe headaches, anxiety, insomnia, and symptoms of Obsessive-Compulsive Disorder (OCD). For this purpose, fluoxetine, topiramate, and nortriptyline were prescribed. Two months after increasing the topiramate dosage to 400 mg per day, she developed OLLs. The Topiramate dose was reduced within two weeks and finally discontinued. The lesions were removed four weeks after the cessation. The patient had no lesions for 6 months. With restarting the drug, the lesion reappeared and finally, ceasing topiramate usage. To conclude, the mentioned lesions are one of the rare complications of this anticonvulsant drug.

The Ophthalmic Side Effects of Topiramate: A Review.

Topiramate (TPM) is a sulfonamide drug with multiple modes of action. It inhibits carbonic anhydrase, blocks sodium channels, enhances potassium channels, and stimulates postsynaptic gamma-aminobutyric acid (GABA) receptors. Pharmacists Joe Gardocki and Bruce Maryanoff synthesized TPM for the first time in 1979. The FDA did not approve it for medical use in the US until 1996. Around 2004, it was authorized for the prevention of migraine headaches.TPM, like any medication, has several side effects. Common aftermaths include weight loss, diarrhea, dizziness, sleepiness, fatigue, and coordination issues. Some people may experience mental health issues like memory problems, confusion, and speech or language difficulties. The most well-known ocular side effects of TPM are choroidal effusion syndrome, angle-closure glaucoma, and myopic shift. Aside from these, other ophthalmic adverse effects may arise in some people, including retinal problems, uveitis, visual field defects, myokymia, and neuro-ophthalmology complications. If such complications are not identified and treated promptly, they can be severe and vision-threatening, potentially leading to permanent blindness.TPM's application as a standalone and adjunctive therapy has increased over time. In 2019, more than 10 million prescriptions of TPM were issued. Due to its extensive use, medical professionals and patients must be aware of its potential repercussions, especially ophthalmic issues. The current review paper likewise makes a step in this direction. This article's primary purpose is to educate readers by providing a comprehensive assessment of the research on TPM's ocular side effects. All the information has been collected via a thorough search of the Google Search Engine and PubMed.

The role of diet in the prevention of migraine attacks

The review provides information concerning the influence of dietary factors and different types of diet on the origin and frequency of migraine headaches according to the up-to-date scientific data. The relevance of the problem is associated with high prevalence of migraine, which is a common cause of disability amongst young people. Gut – brain axis takes a significant place in the pathophysiology of migraine. The concept of a gut-brain axis explains a bidirectional relationship between the gastrointestinal system and the central nervous system. It has been suggested that changes in the gut-brain axis functioning may play a role in the pathogenesis of migraine. The review describes possible mechanisms of gut microbiota involvement in the pathogenesis of migraine. Knowledge of the important role of food triggers in migraine has contributed to the development of a dietary therapeutic strategy for the prevention of migraine headache. The paper contains data concerning possible pathogenetically substantiated effects of various types of diet (elimination, epigenetic, ketogenic) in migraine prevention, given the lack of efficacy and side effects of current migraine drug therapy. The review discusses the possible positive effects of dietary approaches on migraine through their beneficial influence on the intestinal microbiota and functioning of the gut-brain axis. Conclusions. An update on the role of diet in the pathogenesis and prevention of migraine attacks is an extremely important and promising scientific field, which requires further research with the development of personalized approaches taking into account the individual characteristics of each patient.

Overcoming Obstacles in Protein Expression in the Yeast Pichia pastoris: Interviews of Leaders in the Pichia Field.

The yeast Pichia pastoris (also known as Komagataella pastoris) has been used for over 30 years to produce thousands of valuable, heterologous proteins, such as insulin to treat diabetes and antibodies to prevent migraine headaches. Despite its success, there are some common, stubborn problems encountered by research scientists when they try to use the yeast to produce their recombinant proteins. In order to provide those working in this field with strategies to overcome these common obstacles, nine experts in P. pastoris protein expression field were interviewed to create a written review and video (https://www.youtube.com/watch?v=Q1oD6k8CdG8). This review describes how each respected scientist addressed a specific challenge, such as identifying high expression strains, improving secretion efficiency and decreasing hyperglycosylation. Their perspective and practical advice can be a tool to help empower others to express challenging proteins in this popular recombinant host.

Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial

ObjectiveThis study aimed to assess the efficacy of concurrent magnesium-sodium valproate therapy and compare it with either magnesium or sodium valproate alone in migraine prophylaxis.Materials and methodsThis randomized single-center double-blind parallel-group controlled clinical trial study was conducted on migraine patients within the age range of 18–65 years. The subjects with at least four monthly attacks were randomly assigned to group A (n = 82) sodium valproate, group B (n = 70) magnesium with sodium valproate, and group C (n = 70) magnesium. The patients passed a one-month baseline without prophylactic therapy and then received a 3-month treatment. The characteristics of migraine, including frequency, severity, duration of the attacks, and the number of painkillers taken per month, were monthly recorded in each visit. The Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) scores were recorded at the baseline and after 3 months of treatment in each group. Within- and between-group analyses were performed in this study.ResultsThe obtained results revealed a significant reduction in all migraine characteristics in all groups compared to those reported for the baseline (P < 0.001). Intragroup data analysis indicated that there was no statistically significant difference in headache frequency between groups A and B in the third month (P = 0.525); nevertheless, three other parameters showed a significant reduction in group B, compared to those reported for group A in the third month (P < 0.05). On the other hand, group C could not effectively reduce measured parameters in the patients, compared to groups A and B after 3 months (P < 0.001). Furthermore, the MIDAS and HIT-6 scores significantly diminished in groups A, B, and C compared to those reported at the baseline (P < 0.001), and these changes were more significant in groups A and B than in group C (P < 0.001).ConclusionThe obtained results of this study revealed that magnesium could enhance the antimigraine properties of sodium valproate in combination therapy and reduce the required valproate dose for migraine prophylaxis.

Comparison of efficacy and safety of three drugs levetiracetam, sodium valproate, and nortriptyline in the prevention of migraine headache

Background and Aim: Headache is the most common cause of referral to a physician. Two approaches of the migraine treatment include: treat the acute attacks and prevent future attacks. In this regard, the aim of this study was to investigate the effect of three drugs lutiracetam, sodium valproate and nortriptyline in the control of migraine headaches in patients with migraine in Birjand Neurology Clinic. Materials and Methods: This study is a quasi-experimental study. According to the physician, 120 migraine patients were divided into one of three groups: Lutiracetam with a daily dose of 250 mg, sodium valproate 500 mg and nortriptyline 25 mg for 4 weeks. Patientschr('39') information was collected through a questionnaire. Then the data were analyzed by SPSS) Version 16) software by using chi-square, paired t-test, and ANOVA. Results: 120 patients were divided into three groups of 40 patients. The mean age of the subjects was 33±11 years, 53.3% of them were female and 46.7% of them were male. In total, 46.7% of patients had severe headache before taking these three drugs. None of them had severe headache after taking the drug and 77.5% of them had mild headache. Lutiracetam group showed the greatest decrease in headache intensity. (P=0.01). Conclusion: Levetiracetam appears to be more effective than the other two drugs, especially sodium valproate, in reducing different degrees of headache.

Short-term Efficacy and Safety of Topical β-Blockers (Timolol Maleate Ophthalmic Solution, 0.5%) in Acute Migraine

Oral β-blockers used for the prevention of migraine headache are not effective for the treatment of acute pain. Small case series have suggested that topically applied β-blockers may be useful in the management of acute migraine pain, warranting evaluation with randomized clinical trials. To evaluate the short-term efficacy and safety of topically applied timolol maleate ophthalmic solution, 0.5%, compared with topically applied placebo eyedrops in the treatment of acute migraine attacks. In this randomized, masked placebo-controlled crossover trial conducted from May 27, 2015, to August 28, 2017, 50 patients with migraine were randomized to receive either timolol eyedrops, 0.5%, or a placebo eyedrop (carboxymethyl cellulose, 0.5%). After a 3-month treatment period, patients completed a 1-month washout period and were crossed over to receive the opposite treatment for a final 3 months. Analysis was performed on a modified intent-to-treat basis. After random assignment, patients were instructed to use 1 drop of the assigned medication in each eye at the earliest onset of migraine. The main outcome measure was reduction in pain score with treatment. The primary end point was reduction of pain score by 4 points, or to zero, 20 minutes after instillation of the eyedrop. Of the 50 patients, 42 (84%) were females and the mean (SD) age was 27.3 (11.3) years. Of a total of 619 migraine attacks, 284 (46%) were treated with timolol, 271 (44%) were treated with the placebo, and 64 (10%) occurred during the washout period when no study medications were used. Seven patients (14%) withdrew after randomization. A total of 233 of the timolol-treated migraine attacks (82%) were associated with a reduction in pain score by 4 points, or to zero, at 20 minutes compared with 38 of the placebo-treated attacks (14%), with a difference of 68 percentage points (95% CI, 62-74 percentage points). A generalized estimating equation analysis revealed that pain score reduction at 20 minutes was greater in the timolol group compared with the placebo group by a mean (SE) of 4.63 points (0.34) (P < .001). This randomized crossover trial supports consideration of timolol eyedrops in the acute treatment of migraine. Further research is warranted to determine if the improvements observed are sustained for a longer follow-up and with larger groups. CTRI/2015/05/005829, UTN: U1111-1167-6439.

Calcitonin Gene-Related Peptide Antagonists as a Savior in Episodic and Chronic Migraine: A Review.

Headaches due to migraine are the second leading cause of disability in the world. Migraine can be classified as episodic migraine (EM) and chronic migraine (CM). The course of the disease starts from an aura followed by 4-72 hours of bouts of throbbing, mostly unilateral headache associated with nausea, photo/phonophobia with/without neurological deficit. The pathophysiology of migraine remains debatable and many drugs are used to help control migraine attacks with little or no benefit. However, patient compliance remains a reason for over and underdosing of these medications. The calcitonin gene-related peptide (CGRP), a vasoactive peptide is known to contribute to the disease course. Much work is done on antagonizing the receptor or the molecule itself. For this purpose, genetically engineered monoclonal antibodies are being utilized for long-term reduction in morbidity and prevention of migraine headaches. The four to name are: galcanezumab, fremanezumab, eptinezumab, and erenumab. The purpose of this review is to shed light on the use of these monoclonal antibodies, completed and recruiting trials, and the role of these medications in the prevention of not only EM and CM but also in medication overuse headaches.

A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine

Daily oral beta-adrenoreceptor antagonist has been shown to be effective in preventing migraine headaches. Timolol 0.5% ophthalmic solution is a non-selective beta-adrenoreceptor antagonist, where the primary use is for glaucoma. There have been case reports that timolol is effective in aborting or improving an acute migraine headache. The objective of this study was to assess the efficacy (decrease of ≥ 50% in pain scale at 120 minutes) of timolol 0.5% ophthalmic solution compared to placebo in acute treatment of migraine headache. We performed a randomized, double-blind, crossover, placebo-controlled, study. Study entry criteria required subjects to have one to eight migraine episodes per month. The primary outcome was comparison of the change in a visual analog pain scale (VAS) at 120 minutes after taking the study medication. Study subjects were given a pain scale with a range of 1 (no pain) to 10 (most severe pain) to complete after onset of migraine but before administration of study drops and 120 minutes after administration of study drops. Improvement was defined as a ≥ 50% decrease in pain scale. Nineteen subjects completed the study and were used for analysis. The primary outcome changes in pain scale, 120 minutes after dose, showed a similar decrease for placebo and drug with a slightly wider 95% CI for placebo. Six subjects in each arm experienced a ≥ 50% decrease in pain scale. These results support that timolol 0.5% ophthalmic solution is not an efficacious treatment for acute migraine headache.

Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: A phase 2 randomized controlled clinical trial

Objective: This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine. Methods: In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S). Results: The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p &lt; 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo. Conclusion: The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

Development and Characterization of Mucoadhesive Nanoparticles of Topiramate for Nasal Administration

Nasal drug delivery has been recognized as a promising route for delivery of therapeutic compounds including biopharmaceuticals. It has been demonstrated that absorption of drugs can enhance by using absorption enhancers or increasing the drug residence time in the nasal cavity. Mucoadhesive polymers can serve both functions. The residence time in the nasal cavity is considerably increased for nanoparticles compared to solutions. Topiramate (TPM) is used alone or with other medications to prevent and control seizures (epilepsy). This medication is also used to prevent migraine headaches and decrease how often you get them. TPM will not treat a migraine headache once it occurs. The purpose of the present study was to prepare and evaluate mucoadhesive chitosan nanoparticles of TPM for the nasal administration by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as FTIR, particle size, scanning electron microscopy (SEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 45and 62nm exhibited excellent mucoadhesive properties. Stability study at various storage temperature was also done in which the prepared formulation showed an improved stability. The zeta potential of the best chitosan preparation (F4) was found to be -35.5mV, which confirms the stability of prepared nanosuspension. Mucoadhesive chitosan nanoparticles can be a promising carrier for nasal delivery of TPM found to have high encapsulation efficiency and predetermined in vitro release profile. Keywords: Nasal drug delivery, Topiramate, Nanoparticles, ionic gelation method, Migraine headache

New Drugs for Preventing Migraines.

The Food and Drug Administration has approved three drugs from a new drug class designed to prevent migraine headaches. The drugs target calcitonin gene–related peptide, a substance involved in the excessive cerebral vasodilation that leads to migraine headaches.The three new products are administered subcutaneously once per month.

Effects of monoclonal antagonist antibodies on calcitonin gene-related peptide receptor function and trafficking

BackgroundMonoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are efficacious for the prevention of migraine headaches. The downstream molecular mechanisms following ligand-receptor blockade by which these antibodies prevent CGRP signaling through CGRP receptors have not been demonstrated.MethodsHere we produced tool monoclonal functional antagonist antibodies against CGRP and its canonical receptor and developed a novel cellular model using fluorogen-activated protein technology that allows detection of CGRP receptor internalization by flow cytometry and, for an extended time course, visualization by confocal microscopy.ResultsUsing this cell model we showed that these antagonist antibodies block both CGRP-induced cAMP signaling and CGRP receptor internalization. At least 10-fold higher concentrations of either antibody are necessary to block CGRP receptor internalization compared with cAMP accumulation in our cell model.ConclusionThese data reinforce our understanding of how monoclonal functional antagonist antibodies interfere with CGRP signaling.

The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study.

Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache. In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500mg and the control group received valproate sodium 400mg two tablets each day (every 12h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide-valproate) and 32 patients were in group 2 (valproate-magnesium oxide). The mean number of migraine attacks and days per month was 1.72 ± 1.18 and 2.09 ± 1.70, with a mean duration of 15.50 ± 21.80h in magnesium group and 1.27 ± 1.27 and 2.22 ± 1.96, with a mean duration 13.38 ± 14.10 in valproate group. This study has shown that 500mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.