Calcitonin gene-related peptide8-37 antagonizes capsaicin-induced vasodilation in the skin: evaluation of a human in vivo pharmacodynamic model.
J Pharmacol Exp Ther
; 325(1): 248-55, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18216286
ABSTRACT
The purpose of this study was to identify the mediators involved in capsaicin-induced vasodilation in the human skin and to evaluate a pharmacodynamic model for the early clinical evaluation of calcitonin gene-related peptide (CGRP) receptor antagonists. Dermal blood flow (DBF) response of the forearm skin to topically applied capsaicin was measured using laser Doppler perfusion imaging in 22 subjects. The effect of intra-arterially administered CGRP(8-37) (1200 ng . min(-1) . dl(-1) forearm), indomethacin (5 mug . min(-1) . dl(-1) forearm), and N(G)-monomethyl-l-arginine (l-NMMA; 0.2 mg . min(-1) dl(-1) forearm), and orally administered aprepitant (375 mg) on capsaicin-induced dermal vasodilation was assessed. Furthermore, the diurnal variation of the DBF response to capsaicin was studied. CGRP(8-37) inhibited the capsaicin-induced DBF increase 217(145, 290)% in infused versus 370 (254, 486)% in the noninfused arm [mean (95% CI); p = 0.004]. In contrast, indomethacin, l-NMMA, aprepitant, and the time of assessment did not affect the DBF response to capsaicin. Thus, capsaicin-induced vasodilation in the human forearm skin is largely mediated by CGRP, but not by vasodilating prostaglandins, nitric oxide, or substance P. The response to capsaicin does not display a circadian rhythm. A pharmacodynamic model is proposed to evaluate CGRP receptor antagonists in humans in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Pele
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Vasodilatação
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Capsaicina
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Peptídeo Relacionado com Gene de Calcitonina
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Humans
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Middle aged
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Bélgica