Anti-allergic effects of milrinone and sulmazole in isolated rat lungs in comparison with theophylline.
Milrinone and sulmazole, two recently developed drugs, inhibit specific fractions of the phosphodiesterase (PDE) isozyme system. Since theophylline aspecifically inhibits the PDE complex, we compared the effects of milrinone and sulmazole with those of theophylline on antigen-induced bronchoconstriction, vasoconstriction, mediator release and leukotriene production. In the isolated perfused and ventilated lung of actively sensitized rats, we elicited antigen-induced bronchoconstriction, vasoconstriction and release of mediators like histamine, 5-hydroxytryptamine (5-HT) and slow-reacting substance of anaphylaxis (SRS-A). Milrinone, sulmazole and theophylline inhibited antigen-induced bronchoconstriction and vasoconstriction in a dose-dependent manner with minor differences in potency. Antigen-induced release of preformed mediators like histamine and 5-HT was inhibited only at high concentrations of milrinone, whereas sulmazole failed to inhibit mediator release. Theophylline also failed to inhibit 5-HT release. However, SRS-A synthesis was markedly reduced by these drugs in relatively low concentrations. It is concluded that milrinone and sulmazole have anti-allergic effects similar to those of theophylline and that all three PDE inhibitors reduce SRS-A synthesis.
Post
M J
MJ
Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands.
te Biesebeek
J D
JD
van Rooij
H H
HH
Wemer
J
J
Porsius
A J
AJ
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D007093:Imidazoles; D015289:Leukotrienes; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D012701:Serotonin; D013806:Theophylline; C029758:sulmazole; D020105:Milrinone