Effect of Serotonin Antagonists on the Dextran‐induced Anaphylactoid Reaction in the Rat

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Abstract
Dextran injected i.v. into rats causes a rapid lowering of the extent of activation of factor XII and of the plasma levels of prekallikrein and plasminogen, and at the same time a profound fall in blood pressure. The effects on the dextran-induced reactions of 3 serotonin antagonistic lysergic acid derivatives were studied in the rat: bromolysergic acid diethylamide (BOL 148), methysergide and ergotamine. BOL 148 was the only effective inhibitor of the blood pressure fall, having an inhibitory effect over the dose range 1.0-4.0 mg/kg i.v. The finding supports the assumption that part of the dextran-induced blood pressure fall is mediated by serotonin through D-receptors. All 3 serotonin antagonists showed a serotonin-like lowering effect on the activation of factor XII and on the level of prekallikrein in plasma (BOL 148 1.0-4.0 mg/kg; methysergide 0.10-0.60 mg/kg; ergotamine 0.10-0.60 mg/kg). The results with the serotonin antagonists alone and in combination with dextran provided evidence that the serotonin-mediated part of the blood pressure fall can not be secondary to the effect of dextran on the plasma parameters assayed.

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