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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

5-HT2-receptor antagonists: alpha 1- vs. 5-HT2-receptor blocking properties in blood vessels.

LY53857, spiperone, ketanserin, and setoperone were potent and competitive 5-HT2-receptor antagonists in the rat jugular vein with equivalent affinities at 5-HT2 receptors. In the rat jugular vein, ritanserin blocked 5-HT2-mediated contractile responses with a depression of the maximum response in concentrations greater than 3 X 10(-10) M. Ketanserin, spiperone, ritanserin, and setoperone were also alpha 1-adrenergic receptor antagonists, although affinity at alpha 1-adrenergic receptors was less for ritanserin and setoperone than for ketanserin or spiperone. Of the 5-HT2-receptor antagonists examined, LY53857 was the most selective with respect to alpha 1-adrenergic receptor affinity, showing 250,000-fold selectivity as an antagonist at 5-HT2 receptors. The possibility that the dual properties of 5-HT2- and alpha 1-receptor blockade confer greater antihypertensive efficacy than alpha 1-receptor blockade alone was also examined in vivo. However, acute administration of LY53857 at doses sufficient to abolish 5-HT2-receptor activation did not enhance blood pressure reduction produced by the alpha-adrenergic receptor antagonist phentolamine in normotensive or spontaneously hypertensive rats. These data argue against an important role for 5-HT2 receptors in blood pressure regulation even in combination with alpha-adrenergic receptor blockade.[1]

References

  1. 5-HT2-receptor antagonists: alpha 1- vs. 5-HT2-receptor blocking properties in blood vessels. Cohen, M.L., Schenck, K.W., Kurz, K.D. J. Cardiovasc. Pharmacol. (1988) [Pubmed]
 
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