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Analysis of the agonist activity of fenoldopam (SKF 82526) at the vascular 5‐HT 2 receptor
Author(s) -
Christie Mark I.,
Harper Diane,
Smith George W.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13399.x
Subject(s) - fenoldopam , agonist , chemistry , endocrinology , medicine , pharmacology , receptor , receptor antagonist , antagonist , biology , biochemistry
1 The 5‐HT 2 receptor agonist activity of fenoldopam (SKF 82526) was characterized in the rabbit isolated aorta preparation. 2 Fenoldopam was an agonist at the vascular 5‐HT 2 receptor with lower affinity and efficacy than the naturally occurring agonist 5‐hydroxytryptamine (5‐HT). Fenoldopam had an affinity (p K A ) of 5.84 ± 0.04 and efficacy (τ) of 0.57 ± 0.04, whereas 5‐HT had a p K A of 6.65 ± 0.12 and τ of 2.66 ± 0.41. 3 The constrictor effects of fenoldopam and 5‐HT were competitively antagonized by the 5‐HT 2 antagonist, ketanserin, with p K B values of 8.81 ± 0.11 and 8.83 ± 0.10 respectively. 4 Prior incubation with fenoldopam produced a concentration‐related rightward shift of a subsequent 5‐HT concentration‐response curve. This inhibition was specific for 5‐HT since constrictor responses to angiotensin II were unaffected. 5 This study indicates that the D 1 receptor agonist, fenoldopam, acts as an agonist at the vascular 5‐HT 2 receptor, but with an affinity and efficacy less than that of the naturally occurring agonist, 5‐HT.