Comparison of three metrenperone dosage regimens inhibiting the 5-hydroxytryptamine-induced pulmonary dysfunction in...

The effects of a 5-hydroxytryptamine (5-HT) challenge infusion on pulmonary function values were studied in healthy calves, pretreated with varying doses of metrenperone, a selective type 2 serotonergic (5-HT2) antagonist. In the first part of the experiment, the 5-HT challenge was performed 30 minutes after administration of metrenperone at a dose of 0.025 mg kg-1 (group 1, n = 8), 0.050 mg kg-1 (group 2, n = 8) and 0.100 mg kg-1 (group 3, n = 7). In the second part, the 5-HT challenge was performed 12 hours after administration of metrenperone at a dose of 0.050 mg kg-1 (group 4, n = 5) and 0.100 mg kg-1 (group 5, n = 5). None of the three doses of metrenperone influenced the 5-HT-induced ventilatory changes. For the challenge performed 30 minutes after blockade, all three doses inhibited the bronchoconstrictive process triggered by the 5-HT challenge. There was no dose-related inhibition. On the other hand, when the challenge was performed 12 hours after metrenperone, there was a dose-related inhibition with only the higher dose (0.100 mg kg-1) showing a significant efficacy in inhibiting 5-HT-induced bronchoconstriction. It is concluded that, if 5-HT is involved in the pathophysiological processes of respiratory diseases in cattle, a 5-HT2 blockade with metrenperone at a dose rate of 0.100 mg kg-1 and with a dosage interval of 12 hours should improve pulmonary function.