Discovery of (5S,6S,9R)-5-Amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (BMS-927711): An Oral Calcitonin Gene-Related Peptide (CGRP) Antagonist in Clinical Trials for Treating Migraine

2012 ◽  
Vol 55 (23) ◽  
pp. 10644-10651 ◽  
Author(s):  
Guanglin Luo ◽  
Ling Chen ◽  
Charles M. Conway ◽  
Rex Denton ◽  
Deborah Keavy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Antagonist

scholarly journals Calcitonin Gene-Related Peptide Influences Bone-Tendon Interface Healing Through Osteogenesis: Investigation in a Rabbit Partial Patellectomy Model

2021 ◽  
Vol 9 (7) ◽  
pp. 232596712110039
Author(s):  
Huabin Chen ◽  
Hongbin Lu ◽  
Jianjun Huang ◽  
Zhanwen Wang ◽  
Yang Chen ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Bone Mineral ◽  
Calcitonin Gene Related Peptide ◽  
Control Group ◽  
Mineral Density ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Partial Patellectomy ◽  
Antagonist Group ◽  
Cgrp Antagonist

Background: Calcitonin gene-related peptide (CGRP), which has been shown to play an important role in osteogenesis during fracture repair, is also widely distributed throughout the tendon and ligament. Few studies have focused on the role of CGRP in repair of the bone-tendon interface (BTI). Purpose: To explore the effect of CGRP expression on BTI healing in a rabbit partial patellectomy model. Study Design: Controlled laboratory study. Methods: A total of 60 mature rabbits were subjected to a partial patellectomy and then randomly assigned to CGRP, CGRP-antagonist, and control groups. In the CGRP-antagonist group, the CGRP receptor antagonist BIBN4096BS was administered to block CGRP receptors. The patella–patellar tendon complex was harvested at 8 and 16 weeks postoperatively and subjected to radiographic, microlaser Raman spectroscopy, histologic, and biomechanical evaluation. Results: Radiographic data showed that local CGRP expression improved the growth parameters of newly formed bone, including area and volumetric bone mineral density ( P < .05 for both). Raman spectroscopy revealed that the relative bone mineral composition increased in the CGRP group compared with in the control group and the CGRP-antagonist group ( P < .05 for both). Histologic testing revealed that the CGRP group demonstrated better integration, characterized by well-developed trabecular bone expansion from the residual patella and marrow cavity formation, at the 8- and 16-week time points. Mechanical testing demonstrated that the failure load, ultimate strength, and stiffness in the CGRP group were significantly higher than those in the control group ( P < .05 for all), whereas these parameters in the CGRP-antagonist group were significantly lower compared with those in the control group at 16 weeks after surgery ( P < .05 for all). Conclusion: Increasing the local concentration of CGRP in the early stages of BTI healing enhanced osteogenesis in a rabbit partial patellectomy model and promoted healing of the BTI injury, whereas treatment using a CGRP antagonist had the opposite effect. However, exogenous CGRP expression did not induce novel bone remolding. Clinical Relevance: CGRP may have potential as a new therapy for BTI injuries or may be added to postoperative regimens to facilitate healing.

scholarly journals Rimegepant: first novel oral calcitonin gene-related peptide inhibitor for migraine

2020 ◽  
Vol 9 (5) ◽  
pp. 829
Author(s):  
Saravana Kumar Ramasubbu ◽  
Senkadhirdasan Dakshinamurthy ◽  
Sarika Palepu ◽  
Arkapal Bandyopadhyay ◽  
Sathish Kumar Rajendran
Keyword(s):  
Area Under The Curve ◽  
Cardiovascular Effects ◽  
Calcitonin Gene Related Peptide ◽  
Causative Role ◽  
Acute Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Effective Option ◽  
Inflammatory Drugs ◽  
Cgrp Antagonist

Migraine is a neurological condition characterized by intense, debilitating headaches. Symptoms may include nausea, vomiting, numbness or tingling, sensitivity to light and sound. There are multitude of drugs available to treat migraine like triptans, non-steroidal anti-inflammatory drugs, ergots and opioids. But these drugs are associated with adverse effects especially triptans causing cardiovascular effects limiting its use. During last decade, calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for management of migraine. CGRP has been shown to release during episode of migraine attack and it may play a causative role in induction of migraine. Rimegepant is a novel CGRP antagonist has been approved by FDA for treatment of acute migraine. Rimegepant is a first oral CGRP antagonist compared to other gepants. The oral bioavailability of Rimegepant is 64% and high fat meal can decrease the Cmax, Tmax and area under the curve. This drug is mainly metabolized by CYP3A4 and to lesser extent by CYP2C9. Most common adverse reactions associated with this drug were nausea and urinary tract infection. Clinical trials for Rimegepant have been positive, and results suggest that the drug may be a new safe and effective option for treatment of acute migraine.

scholarly journals Ubrogepant: First Approval

Drugs ◽  
2020 ◽  
Vol 80 (3) ◽  
pp. 323-328 ◽  
Author(s):  
Lesley J. Scott
Keyword(s):  
Small Molecule ◽  
Acute Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Aura ◽  
Related Peptide ◽  
Global Approval ◽  
Calcitonin Gene ◽  
The Usa ◽  
Cgrp Antagonist

Abstract Ubrogepant (Ubrelvy™) is an orally administered, small molecule, highly-selective, calcitonin gene-related peptide (CGRP) antagonist that was developed by Allergan under license to Merck & Co. as an acute treatment for migraine. In December 2019, ubrogepant received its first global approval in the USA for the acute treatment of migraine (± aura) in adults. This article summarizes the milestones in the development of ubrogepant leading to its first global approval for the acute treatment of migraine (± aura) in adults.

Fremanezumab autoinjector pen for the prevention of migraine

2021 ◽  
Author(s):  
Mark W Weatherall
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Calcitonin Gene Related Peptide ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Related Peptide ◽  
Phase Iii Clinical Trials ◽  
Humanized Monoclonal Antibody ◽  
Calcitonin Gene ◽  
Favorable Tolerability Profile

Ajovy (fremanezumab, Teva Pharmaceuticals, Israel) is a fully humanized monoclonal antibody that selectively binds both isoforms of the calcitonin gene-related peptide. Calcitonin gene-related peptide is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events in migraine. It is indicated for prophylaxis of migraine in adults who have at least four migraine days per month, and can be administered as a subcutaneous injection using an autoinjector device, with two dosing options: 225 mg once a month or 675 mg quarterly. In this article, I present data from Phase III clinical trials of fremanezumab in episodic and chronic migraine, in which fremanezumab demonstrated efficacy and had a favorable tolerability profile, with no serious treatment-related adverse events.

The calcitonin gene-related peptide (CGRP) antagonist CGRP8–37 blocks vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to CGRP

2001 ◽  
Vol 310 (2-3) ◽  
pp. 169-172 ◽  
Author(s):  
Duc Quyen Chu ◽  
Steve Legon ◽  
David M Smith ◽  
Soraia K.P Costa ◽  
Frank Cuttitta ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Skin Involvement ◽  
Rat Skin ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Antagonist

Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI2in rats

2004 ◽  
Vol 286 (1) ◽  
pp. G68-G75 ◽  
Author(s):  
Takeo Saeki ◽  
Takashi Ohno ◽  
Kazuhisa Kamata ◽  
Katsuharu Arai ◽  
Sumito Mizuguchi ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Mucosal Injury ◽  
Inhibitory Effect ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Beraprost Sodium ◽  
Calcitonin Gene ◽  
Microcirculatory Disturbances ◽  
Mild Irritant ◽  
Cgrp Antagonist

Pretreatment with a mild irritant such as 1 M NaCl prevented ethanol-induced mucosal injury, which was abolished by indomethacin, suggesting involvement of endogenous PGs. With the use of intravital microscopy, we investigated the mechanism in microcirculation whereby a mild irritant prevents ethanol-induced mucosal injury. Microcirculation of the basal part of gastric mucosa in anesthetized rats was observed through a window with transillumination. Diameters of arterioles, collecting venules, and venules were measured with an electric microscaler. One molar NaCl alone caused dilation of arterioles and constrictions of collecting venules and venules, which were inhibited by indomethacin. Ethanol (50%) applied to mucosa constricted collecting venules and venules but dilated arterioles. Constriction of collecting venules resulted in mucosal congestion. Pretreatment with 1 M NaCl inhibited ethanol-induced constrictions of collecting venules and venules, and administration of indomethacin or a calcitonin gene-related peptide (CGRP) antagonist, CGRP-(8–37), abolished elimination of constrictions. Topical application (1 nM–10 μM) of PGE2or beraprost sodium (a PGI2analog) to microvasculature markedly and dose-dependently dilated arterioles, whereas that of PGE2, but not beraprost, slightly constricted collecting venules. Pretreatment of microvasculature with a nonvasoactive concentration of PGE2(100 nM) or beraprost (1 nM) completely inhibited ethanol-induced constriction of collecting venules. The inhibitory effect of beraprost but not of PGE2was abolished by CGRP-(8–37). Present results suggest that the mechanism whereby 1 M NaCl prevents ethanol-induced injury is elimination of constrictions of collecting venules and venules by CGRP whose release may be enhanced by PGI2but not by PGE2.

scholarly journals Effects of Anti-Calcitonin Gene-Related Peptide for Migraines: A Systematic Review with Meta-Analysis of Randomized Clinical Trials

2019 ◽  
Vol 20 (14) ◽  
pp. 3527 ◽  
Author(s):  
I-Hsin Huang ◽  
Po-Chien Wu ◽  
En-Yuan Lin ◽  
Chien-Yu Chen ◽  
Yi-No Kang
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Long Term Effect ◽  
Calcitonin Gene ◽  
Quantitative Synthesis

We aimed to evaluate the response rate of migraines by using anti-calcitonin gene-related peptide (anti-CGRP) for patients with migraines. We searched three main medical databases up to 29 March 2019. No restriction on language and publication time were applied. Eligible trials included randomized clinical trials investigating a 50%, 75%, and 100% response rate of migraine patients after anti-CGRP intervention. The collected data were dichotomous, and risk ratios (RRs) with a 95% confidence interval (CI) were used to present the quantitative synthesis results. The systematic review identified 16 eligible randomized clinical trials (RCTs) with 9439 patients. Eight of the 16 trials with 2516 patients reported a 50% response rate, and the pooled results showed a significant benefit from anti-CGRP. However, the effects seem to gradually reduce from the first month (RR 1.99, 95% CI 1.59 to 2.49) to the third month (RR 1.48, 95% CI 1.26 to 1.75) of treatment. The magnitude of effect was influenced by the type of anti-CGRP, according to the test for differences between subgroups (I-square = 53%). The funnel plots and Egger’s tests did not show serious small study effects in the results. In conclusion, the current evidences confirmed that anti-CGRP treatment can reduce migraine pain in the short term (within three months), but the long-term effect should be investigated in the future. Moreover, its effects may be influenced by the type and dose of anti-CGRP. Therefore, future studies should make direct comparisons among anti-CGRP medications.

scholarly journals New CGRP Antagonists

2001 ◽  
Vol 1 ◽  
pp. 16-16
Author(s):  
H. N. Doods ◽  
M. Schindler
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Antagonist

The presentation will focus on BIBN 4096 BS, since this compound is still the only potent calcitonin gene-related peptide (CGRP)-antagonist described so far[1].

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