ArticleHeadache2022
Characterization of transit rates in the large intestine of mice following treatment with a CGRP antibody, CGRP receptor antibody, and small molecule CGRP receptor antagonists.
Article in Headache, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- A Glutamatergic Medial Prefrontal Cortex-Locus Coeruleus Circuit Drives Intestinal Dysmotility in Diarrhea-Predominant Irritable Bowel Syndrome.International journal of molecular sciences · 2026Article
- Influence of Constipation in the Behavior of Circulating Alpha- and Beta-CGRP Levels in Chronic/High-Frequency Migraine Patients After CGRP Monoclonal Antibodies.Biomedicines · 2025Article
- Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice.Scientific reports · 2024Article
- Pharmacological characterisation of erenumab, Aimovig, at two calcitonin gene-related peptide responsive receptors.British journal of pharmacology · 2024Article
- Update of Gepants in the Treatment of Chronic Migraine.Current pain and headache reports · 2023Review
- Mode and site of action of therapies targeting CGRP signaling.The journal of headache and pain · 2023Review
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo characterize the effects of blocking calcitonin gene-related peptide (CGRP) activity in a mouse model of gastrointestinal transport.
backgroundMigraine management using CGRP modulating therapies can cause constipation of varying frequency and severity. This variation might be due to the different mechanisms through which therapies block CGRP activity (e.g., blocking CGRP, or the CGRP receptor) with antibodies or receptor antagonists. The charcoal meal gastrointestinal transit assay was used to characterize constipation produced by these modes of therapy in transgenic mice expressing the human receptor activity-modifying protein 1 (hRAMP1) subunit of the CGRP receptor complex.
methodsMale and female hRAMP1 mice were dosed with compound or vehicle and challenged with a charcoal meal suspension via oral gavage. The mice were then humanely euthanized and the proportion of the length of the large intestine that the charcoal meal had traveled indicated gastrointestinal transit.
resultsAntibody to the CGRP receptor produced % distance traveled (mean ± standard deviation) of 31.8 ± 8.2 (4 mg/kg; p = 0.001) and 33.2 ± 6.0 (30 mg/kg; p < 0.001) compared to 49.7 ± 8.3 (control) in female mice (n = 6-8), and 35.6 ± 13.5 (30 mg/kg, p = 0.019) compared to 50.2 ± 14.0 (control) in male mice (n = 10). Telcagepant (5 mg/kg, n = 8) resulted in % travel of 30.6 ± 14.7 versus 41.2 ± 8.3 (vehicle; p = 0.013) in male mice. Atogepant (3 mg/kg, n = 9) resulted in % travel of 30.6 ± 12.0, versus 41.2 ± 3.7 (control; p = 0.030) in female mice. The CGRP antibody galcanezumab (n = 7-10; p = 0.958 and p = 0.929) did not have a statistically significant effect.
conclusionsThese results are consistent with reported clinical data. Selectively blocking the CGRP receptor may have a greater impact on gastrointestinal transit than attenuating the activity of the ligand CGRP. This differential effect may be related to physiologically opposing mechanisms between the CGRP and AMY1 receptors, as the CGRP ligand antibody could inhibit the effects of CGRP at both the CGRP and AMY1 receptors.
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