Divergent effects of pirenperone, a 5-HT2 antagonist, on the pressor and tachycardic responses to 5-HT in guinea-pigs.

The effects of pirenperone and cyproheptadine on the pressor and tachycardic responses to 5-hydroxytryptamine (5-HT) and to dimethylphenylpiperazinium (DMPP) were compared. Both 5-HT antagonists suppressed in a dose-dependent manner the pressor effect of 5-HT, whilst did not noticeably affect the tachycardic effect of 5-HT and the cardiovascular effects of DMPP. On the molecular base, pirenperone was 15 times more potent antagonist of the pressor response to 5-HT than cyproheptadine. It is concluded that not only the 5-HT receptors in arterial smooth muscle but also the 5-HT receptors in sympathetic ganglia and the adrenal medulla responsible for the pressor response to 5-HT are sensitive to the 5-HT antagonists and probably analogous to the central 5-HT2 receptors. The 5-HT receptors in cardiac tissue mediating tachycardia differ in their pharmacological properties from those in arterial smooth muscle responsible for contraction. It is suggested that the ganglionic components of the pressor and tachycardic responses to 5-HT are mediated via different populations of 5-HT receptors in sympathetic ganglia.