Suppression of histamine-induced tachypnoea in the rhesus monkey by sibenadet: no role for dopamine D2 receptors.
1. Sibenadet (Viozan), a dual dopamine D(2)/beta(2)-adrenoceptor agonist, suppresses histamine-induced tachypnoea in the dog by activating dopamine D(2) receptors. We here compare the effects of sibenadet and formoterol, a selective beta(2)-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 D(2) receptor agonist, quinagolide, did not suppress tachypnoea to histamine despite inducing a fall in blood pressure indicating activation of dopamine D(2) receptors. 6. Thus, both sibenadet and formoterol suppress histamine-evoked tachypnoea in the rhesus monkey. The effect arises exclusively through activation of beta(2)-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.
Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel CH-4002, Switzerland.
J R
JR
Fozard
H
H
Buescher
D C
DC
Farr
L
L
Mazzoni
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D016085:Bronchoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D016210:Methacholine Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D018927:Anti-Asthmatic Agents; D016085:Bronchoconstrictor Agents; D018491:Dopamine Agonists; D004983:Ethanolamines; D006633:Histamine Antagonists; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D016210:Methacholine Chloride; D006632:Histamine; C116267:sibenadet; D000068759:Formoterol Fumarate