Identification and Pharmacological Characterization of Domains Involved in Binding of CGRP Receptor Antagonists to the Calcitonin-like Receptor

Biochemistry ◽  
2006 ◽  
Vol 45 (6) ◽  
pp. 1881-1887 ◽  
Author(s):  
Christopher A. Salvatore ◽  
John J. Mallee ◽  
Ian M. Bell ◽  
C. Blair Zartman ◽  
Theresa M. Williams ◽  
...  
Keyword(s):  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Pharmacological Characterization ◽  
Cgrp Receptor Antagonists

The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1

2012 ◽  
Vol 22 (14) ◽  
pp. 4723-4727 ◽  
Author(s):  
Xiaojun Han ◽  
Rita L. Civiello ◽  
Charles M. Conway ◽  
Deborah A. Cook ◽  
Carl D. Davis ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists

scholarly journals Effect of Calcitonin Gene-Related Peptide Receptor Antagonists on Migraine Treatment: A Meta-Analysis

2021 ◽  
Author(s):  
Jiyoung Kim ◽  
Kyoungjune Pak ◽  
Gha-Hyun Lee ◽  
Jae Wook Cho ◽  
Hyun-Woo kim
Keyword(s):  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Treatment ◽  
Acute Migraine ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Acute Migraine Treatment

Abstract Background: The pathophysiology of migraine has been researched incessantly, and it has been suggested that calcitonin gene-related peptide (CGRP) is associated with migraine attacks. CGRP receptor blockers are attracting attention for migraine prevention and treatment of acute episodes, and CGRP receptor antagonists have been shown to be effective in treating acute migraine headaches. This meta-analysis aimed to assess the effect of available CGRP receptor antagonists, focusing on their therapeutic doses for acute migraine treatment.Methods: We performed a systematic search of MEDLINE (from inception to March 2021) and EMBASE (from inception to March 2021) for English publications using the keywords “migraine” and “Calcitonin gene-related peptide,” limited to human studies.Results: Five studies that focused on examining the effects of CGRP receptor antagonists on acute migraine treatment met the eligibility criteria for this meta-analysis. The pooled analysis demonstrated that the CGRP receptor antagonist improved freedom from pain (OR=2.066, 95% confidence interval [CI] 1.766–2.418, I2=0%), absence of bothersome symptoms (OR=1.606, 95% CI=1.408–1.830, I2=0%), pain relief (OR=1.791, 95% CI=1.598–2.008, I2=0%), and freedom from nausea (OR=1.361, 95% CI=1.196–1.548, I2=0%), significantly more than the placebo. Conclusions: CGRP receptor antagonists are effective for acute migraine treatment and are expected to be used clinically as emerging therapeutic agents.

Quinine analogs as non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists

1997 ◽  
Vol 7 (20) ◽  
pp. 2673-2676 ◽  
Author(s):  
Robert A. Daines ◽  
Kelvin K.C. Sham ◽  
Jack J. Taggart ◽  
William D. Kingsbury ◽  
James Chan ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists

scholarly journals Mechanistic Investigations Support Liver Safety of Ubrogepant

2020 ◽  
Vol 177 (1) ◽  
pp. 84-93 ◽  
Author(s):  
Brenda Smith ◽  
Josh Rowe ◽  
Paul B Watkins ◽  
Messoud Ashina ◽  
Jeffrey L Woodhead ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Liver Toxicity ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Drug Induced ◽  
Clinical Dose ◽  
Liver Safety ◽  
Trial Experience ◽  
Dosing Regimens ◽  
Cgrp Receptor Antagonists

Abstract Small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated therapeutic efficacy for the treatment of migraine. However, previously investigated CGRP receptor antagonists, telcagepant and MK-3207, were discontinued during clinical development because of concerns about drug-induced liver injury. A subsequent effort to identify novel CGRP receptor antagonists less likely to cause hepatotoxicity led to the development of ubrogepant. The selection of ubrogepant, following a series of mechanistic studies conducted with MK-3207 and telcagepant, was focused on key structural modifications suggesting that ubrogepant was less prone to forming reactive metabolites than previous compounds. The potential for each drug to cause liver toxicity was subsequently assessed using a quantitative systems toxicology approach (DILIsym) that incorporates quantitative assessments of mitochondrial dysfunction, disruption of bile acid homeostasis, and oxidative stress, along with estimates of dose-dependent drug exposure to and within liver cells. DILIsym successfully modeled liver toxicity for telcagepant and MK-3207 at the dosing regimens used in clinical trials. In contrast, DILIsym predicted no hepatotoxicity during treatment with ubrogepant, even at daily doses up to 1000 mg (10-fold higher than the approved clinical dose of 100 mg). These predictions are consistent with clinical trial experience showing that ubrogepant has lower potential to cause hepatotoxicity than has been observed with telcagepant and MK-3207.

ChemInform Abstract: Quinine Analogues as Non-Peptide Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists.

ChemInform ◽  
2010 ◽  
Vol 29 (6) ◽  
pp. no-no ◽  
Author(s):  
R. A. DAINES ◽  
K. K. C. SHAM ◽  
J. J. TAGGART ◽  
W. D. KINGSBURY ◽  
J. CHAN ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists
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