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• W2121098678 abstract "Objectives The aims of this study were to assess the potential of CGRP8–37, the C-terminal fragment of calcitonin gene–related peptide (CGRP), to inhibit CGRP-induced vasodilation in the human forearm and to evaluate a pharmacodynamic model to aid the clinical development of novel CGRP-receptor antagonists. Methods Forearm blood flow (FBF) responses to intra-arterial CGRP infusions were measured via venous occlusion plethysmography in 21 healthy subjects. Dose response to CGRP was assessed during graded infusion of CGRP (1, 3, and 10 ng·min−1·dL−1 forearm; n = 6). After a 90–minute washout period, CGRP infusions were repeated during coinfusion of CGRP8-37 (333 ng·min−1·dL−1 forearm) to assess inhibition by CGRP8-37. To determine the antagonistic potency of CGRP8-37, a 4-period, placebo-controlled crossover study was conducted in 6 subjects, in which CGRP (10 ng·min−1·dL−1 forearm) was infused for 20 minutes together with placebo or CGRP8-37 (300, 600, or 1200 ng·min−1·dL−1 forearm). In addition, the effect of each dose of CGRP8-37 on resting FBF was evaluated. Results CGRP8–37 significantly inhibited the CGRP-induced increase in FBF compared with placebo (from 3.2 ± 1.1 mL·min−1·dL−1 forearm at baseline to 4.8 ± 1.0, 7.7 ± 1.9, and 12.3 ± 3.8 mL·min−1·dL−1 forearm versus 3.1 ± 0.7 mL·min−1·dL−1 forearm to 3.8 ± 0.6, 5.2 ± 1.5, and 8.5 ± 3.0 mL·min−1·dL−1 forearm for placebo and CGRP8-37, respectively; P < .001). The FBF response during the 20-minute infusion of CGRP was dose-dependently inhibited by CGRP8-37 (area under the curve, 200 ± 51 mL·dL−1 forearm for placebo versus 181 ± 23, 160 ± 40, and 132 ± 56 mL·dL−1 forearm for CGRP8-37, 300, 600, and 1200 ng·min−1·dL−1 forearm, respectively; P < .001). CGRP8-37 did not affect resting FBF. Conclusions CGRP8–37 inhibits CGRP-induced vasodilation in the human forearm without affecting resting FBF. Venous occlusion plethysmography combined with brachial artery administration of CGRP provides a suitable pharmacodynamic model to aid the clinical development of CGRP-receptor antagonists. Clinical Pharmacology & Therapeutics (2006) 79, 263–273; doi: 10.1016/j.clpt.2005.11.005" @default.
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• W2121098678 date "2006-03-01" @default.
• W2121098678 modified "2023-09-27" @default.
• W2121098678 title "Calcitonin gene–related peptide–induced vasodilation in the human forearm is antagonized by CGRP8-37: Evaluation of a human in vivo pharmacodynamic model" @default.
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• W2121098678 doi "https://doi.org/10.1016/j.clpt.2005.11.005" @default.
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