A Short on Ubrogepant

Migraine is a mysterious disorder characterized by pulsating head ache, which is actually characterized to one side and comes in attacks which will be lasting for about 3-48 hours and can be associated with nausea,vomiting,sensitivity to sound,flashes of light,vertigoand diarrhoea [1]. Most of the drugs which are in current use for actue migraine like triptans, treats the disorder symptomatically. A novel group of drugs has been in research for the migraine which treats the disorder pathologically. Calcitonin gene – related peptide (CGRP) has a major role in the pathophysiology of the disorder and hence CGRP receptor antagonist, known as Gepants are in the research process [2]. Gepants are being studied for the efficacy of treating acute migraine [2]. This article will be a review article about the drug – Ubrogepant, which is approved for treatment of migraine with acute attacks in adults [3].

Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist for Abortive Migraine Treatment

Objective To review the pharmacology, efficacy, and safety of ubrogepant as an abortive migraine treatment. Data Sources A literature search of MEDLINE and PubMed was performed (January 2006 through May 2021) using the following search terms: ubrogepant, calcitonin gene related peptide, and abortive migraine therapy. Study Selection and Data Extraction Relevant studies evaluating ubrogepant’s pharmacology, efficacy, and safety in humans for the treatment of migraine were considered Data Synthesis Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved by the Food and Drug Administration for the acute treatment of migraine via data from ACHIEVE I and II. From ACHIEVE I, ubrogepant demonstrated superiority to placebo in freedom from migraine pain at 2 hours postdose (50-mg dose: odds ratio [OR] = 1.83, 95% CI = 1.25-2.66; 100-mg dose: OR = 2.04, 95% CI = 1.41-2.95) and freedom from most bothersome symptom (MBS; 50-mg dose: OR = 1.70, 95% CI = 1.27-2.28; 100-mg dose: OR = 1.63, 95% CI = 1.22-2.17). ACHIEVE II trial demonstrated efficacy of ubrogepant 50 mg compared with placebo (2-hour pain freedom: OR = 1.62, 95% CI = 1.14-2.29; 2-hour MBS freedom: OR = 1.65, 95% CI = 1.25-2.20). Relevance to Patient Care and Clinical Practice Ubrogepant is a viable option for patients who are unable to tolerate nonsteroidal anti-inflammatory drug or triptan therapy because of ineffective relief or contraindications that limit use. Conclusions Ubrogepant is a well-tolerated effective abortive migraine treatment that bridges a gap in therapy for many patients who previously could not tolerate other first-line treatments.

Stability Indicating Analytical Method Development and Validation for the Estimation of Rimegepant in Bulk and Its Tablets Using Rp-HPLC

Aim: Ramegepant is a novel molecule belongs to the class of calcitonin gene – related peptide (CGRP) receptor antagonist, which was developed for the prevention and treatment of migraine. Ramegepant was reported to act at the CGRP receptor with good oral bioavailability. The objective of this study was to develop a simple and fast stability indicating method for the determination of Ramegepant in bulk and tablets. Methodology: Ramegepant was eluted on a Waters C18 Column with 250 mm × 4.6 mm i.d and 5 μm Particle size with a mobile phase of Potassium dihydrogen orthophosphate buffer pH 7.0 : Methanol 30:70 v/v in isocratic mode at a flow rate of 0.8 ml/min. The analyte was quantified using a 272 nm PDA detector. Results: The chromatograms of Ramegepant obtained with this method showed a well resolved retention time at 3.29 min of its excipients and degradation products. The area of ​​the peak with respect to the concentration calibration curves, which were linear from 70 to 210 µg / ml, had a regression coefficient (r2) greater than 0.999. Accuracy and precision have been determined and perfectly matched to the ICH standards. Conclusion: The study showed that the proposed Rp-HPLC method was simple, fast, robust and reproducible, which can be used for the evaluation of the purity and stability of the drug without interference from excipients or decomposition products of active pharmaceutical ingredients.

Novel Therapies in Acute Migraine Management: Small-Molecule Calcitonin Gene-Receptor Antagonists and Serotonin 1F Receptor Agonist

Objective To review the efficacy, safety, and cost of 3 newly approved agents—ubrogepant, lasmiditan, and rimegepant—representing 2 therapeutic classes, calcitonin gene-related peptide (CGRP) receptor antagonist and serotonin 1F (5-HT1F) agonists, for the acute treatment of migraine with or without aura. Data Sources The Institute of Health US National Library of Medicine Clinical Trials, PubMed, and Cochrane databases were queried. Abstracts, journal articles, and other relevant sources published or present were reviewed. Search terms included the following: ubrogepant, MK-1602, Ubrelvy®, rimegepant, Nurtec®, BHV-3000, BMS-927711, lasmiditan, Reyvow®, LY573144. Study Selection and Data Extraction Relevant English-language articles from June 30, 2010, to August 31, 2020, were evaluated and included in the narrative. Data Synthesis CGRP receptor antagonists, ubrogepant and rimegepant, achieved 2-hour pain freedom and freedom from the most bothersome migraine symptom (MBS) at 2 hours. Both agents were well tolerated, with adverse effects similar to placebo. Lasmiditan, a 5-HT1F receptor antagonist, also improved 2-hour pain freedom and freedom from the MBS at 2 hours. Lasmiditan is associated with dizziness, paresthesia, somnolence, nausea, fatigue, and lethargy. Relevance to Patient Care and Clinical Practice Ubrogepant, rimegepant, and lasmiditan represent a new and exciting chapter in acute migraine therapy. To date, no head-to-head studies have compared these agents with the triptans. Ubrogepant and lasmiditan are effective in triptan nonresponders. None of the 3 agents is contraindicated in cardiovascular disease, unlike the triptans. Conclusions Based on available data, ubrogepant, rimegepant, and lasmiditan should be reserved as second-line therapy and may be safe in patients with cardiovascular risk. Lasmiditan’s adverse effect profile may limit its use.

Localization of TRPA1 channels and characterization of TRPA1 mediated responses in dural and pial arteries in vivo after intracarotid infusion of Na2S

Background The Transient Receptor Potential Ankyrin 1 (TRPA1) channel might play a role in migraine. However, different mechanisms for this have been suggested. The purpose of our study was to investigate the localization and significance of TRPA1 channels in rat pial and dural arteries. Methods Immunofluorescence microscopy was used to localize TRPA1 channels in dural arteries, pial arteries, dura mater and trigeminal ganglion. The genuine closed cranial window model was used to examine the effect of Na2S, a donor of the TRPA1 channel opener H2S, on the diameter of pial and dural arteries. Further, we performed blocking experiments with TRPA1 antagonist HC-030031, calcitonin gene-related peptide (CGRP) receptor antagonist olcegepant and KCa3.1 channel blocker TRAM-34. Results TRPA1 channels were localized to the endothelium of both dural and pial arteries and in nerve fibers in dura mater. Further, we found TRPA1 expression in the membrane of trigeminal ganglia neuronal cells, some of them also staining for CGRP. Na2S caused dilation of both dural and pial arteries. In dural arteries, this was inhibited by HC-030031 and olcegepant. In pial arteries, the dilation was inhibited by TRAM-34, suggesting involvement of the KCa3.1 channel. Conclusion Na2S causes a TRPA1- and CGRP-dependent dilation of dural arteries and a KCa3.1 channel-dependent dilation of pial arteries in rats.