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Suppression of histamine-induced tachypnoea in the rhesus monkey by sibenadet: no role for dopamine D2 receptors

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Summary

1 Sibenadet (Viozan®), a dual dopamine D2/β2-adrenoceptor agonist, suppresses histamine-induced tachypnoea in the dog by activating dopamine D2 receptors. We here compare the effects of sibenadet and formoterol, a selective β2-adrenoceptor agonist, on histamine-induced tachypnoea in the rhesus monkey.

2 Anaesthetized, spontaneously breathing, rhesus monkeys were set up for measuring airways resistance, respiratory rate, blood pressure and heart rate.

3 Both sibenadet and formoterol administered by aerosol, induced inhibition of the bronchoconstrictor response to aerosolized methacholine accompanied by tachycardia. Sibenadet, but not formoterol, also reduced blood pressure.

4 Administration of histamine by inhalation induced tachypnoea which was accompanied by bronchoconstriction. Tachypnoea to histamine was suppressed by both sibenadet and formoterol at doses which manifest anti-bronchoconstrictor activity. These effects and the accompanying tachycardia but not the hypotension induced by sibenadet were abolished by pretreatment with propranolol.

5 The dopamine D2 receptor agonist, quinagolide, did not suppress tachypnoea to histamine despite inducing a fall in blood pressure indicating activation of dopamine D2 receptors.

6 Thus, both sibenadet and formoterol suppress histamine-evoked tachypnoea in the rhesus monkey. The effect arises exclusively through activation of β2-adrenoceptors and probably reflects the anti-bronchoconstrictor effects of these agents. The results reveal a fundamental difference in the role of dopamine receptors in the airways of dog and rhesus monkey.
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Keywords: dopamine D2 receptors; formoterol; histamine-induced tachypnoea; rhesus monkey; sibenadet; β2-adrenoceptors

Document Type: Research Article

Publication date: 2004-01-01

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