Cardiovascular studies with SK&F 93319, an antagonist of histamine at both H1‐ and H2‐receptors

Abstract

1 Cardiovascular studies have been made in anaesthetized cats with SK&F 93319, an antagonist of histamine at both H₁- and H₂-receptors. 2 SK&F 93319, 8 × 10⁻⁸ and 4 × 10⁻⁷ mol kg⁻¹ min⁻¹ antagonized depressor responses to injections of histamine and the maximum displacement of histamine dose-response curves exceeded that which can be obtained with either an H₁-receptor antagonist or an H₂-receptor antagonist alone. 3 SK&F 93319, 8 × 10⁻⁸ and 4 × 10⁻⁷ mol kg⁻¹ min⁻¹, also caused dose-dependent antagonism of histamine-induced falls in blood pressure and total peripheral resistance during intravenous infusions of histamine. 4 SK&F 93319 inhibited depressor responses to intravenous injections of 2-(2-aminoethyl)pyridine, dimaprit and impromidine. The displacement of the 2-(2-aminoethyl)pyridine dose-response curve was similar to the displacement of histamine dose-response curves. SK&F 93319 caused greater displacement of dimaprit or impromidine dose-response curves than of histamine or 2-(2-aminoethyl)pyridine dose-response curves. 5 SK&F 93319 was an effective antagonist of histamine, 2-(2-aminoethyl)pyridine or dimaprit-induced vasodilatation in femoral and gastric vasculature. 6 SK&F 93319 has been shown to be an effective antagonist of vascular responses to histamine in anaesthetized cats. SK&F 93319 appeared to be more effective as an H₂-receptor antagonist than as an H₁-receptor antagonist in these vascular studies.