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In vivo and in vitro activity of selective 5‐hydroxytryptamine 2 receptor antagonists
Author(s) -
Conolan Sean,
Quinn Michael J.,
Taylor David A.
Publication year - 1986
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.1476-5381.1986.tb11128.x
Subject(s) - ketanserin , ritanserin , in vivo , chemistry , blood pressure , endocrinology , pharmacology , medicine , vasoconstriction , 5 ht receptor , receptor , serotonin , biology , microbiology and biotechnology
1 The abilities of ketanserin, ritanserin, R56413 and LY53857 to inhibit 5‐hydroxytryptamine (5‐ HT) and noradrenaline‐induced vasoconstrictor responses both in vitro and in vivo and to lower blood pressure in the rat, were compared. 2 In the isolated perfused mesenteric artery preparation of the rat all of the compounds tested were found to be potent inhibitors of 5‐HT‐induced vasoconstrictor responses. Ritanserin was the most potent compound, producing more than 50% inhibition of a near maximal response to 5‐HT at a concentration of 10 −11 M. All four compounds were found to be competitive antagonists of noradrenaline; ketanserin being the most potent with a pA 2 value of 7.64 ± 0.06. 3 5‐HT‐induced pressor responses in the pithed rat were inhibited by low doses (0.3–10 μg kg −1 ) of the four compounds. Ketanserin, at doses of 0.1–3.0 mg kg −1 , resulted in rightward shifts of the control dose‐response curve to noradrenaline in the pithed rat. None of the other compounds had any significant effect on the noradrenaline‐induced pressor responses. 4 Ketanserin (0.1–1 mg kg −1 ) produced a dose‐dependent decrease in the mean arterial blood pressure of anaesthetized rats. The maximum decrease in blood pressure observed following a dose of 1 mg kg −1 ketanserin was 73.7 ± 4.7 mmHg. The other compounds at doses of 1.0–3.0 mg kg −1 produced a decrease in blood pressure of a lesser magnitude than that following ketanserin. In addition, this effect did not appear to be dose‐dependent. 5 It is suggested that the acute hypotensive effect of ketanserin results predominantly from α 1 ‐adrenoceptor blockade. The involvement of antagonism of 5‐HT 2 receptors in the hypotensive effect of the other compounds tested cannot be excluded.