| Autor: |
de Vries T; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Boucherie DM; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., van den Bogaerdt A; ETB-BISLIFE, Heart Valve Department, 1940 Beverwijk, The Netherlands., Danser AHJ; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., MaassenVanDenBrink A; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. |
| Jazyk: |
angličtina |
| Zdroj: |
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Jul 28; Vol. 16 (8). Date of Electronic Publication: 2023 Jul 28. |
| DOI: |
10.3390/ph16081075 |
| Abstrakt: |
Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for the treatment of migraine. Here, the effect of the small-molecule CGRP receptor antagonist zavegepant (0.1 nM-1 µM) on CGRP-induced relaxation in isolated human coronary arteries (HCAs) was investigated. A Schild plot was constructed and a pA 2 value was calculated to determine the potency of zavegepant. The potency and Schild plot slopes of atogepant, olcegepant, rimegepant, telcagepant, ubrogepant and zavegepant in HCAs and human middle meningeal arteries (HMMAs), obtained from our earlier studies, were compared. Zavegepant shifted the concentration-response curve to CGRP in HCAs. The corresponding Schild plot slope was not different from unity, resulting in a pA 2 value of 9.92 ± 0.24. No potency difference between HCAs and HMMAs was observed. Interestingly, olcegepant, atogepant and rimegepant, with a Schild plot slope < 1 in HCAs, were all >1 log unit more potent in HMMAs than in HCAs, while telcagepant, ubrogepant and zavegepant, with a Schild plot slope not different from unity, showed similar (<1 log difference) potency across both tissues. As a Schild plot slope < 1 may point to the involvement of multiple receptors, it is important to further identify the receptors involved in the relaxation to CGRP in HCAs, which may be used to improve the cardiovascular safety of future antimigraine drugs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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