Enoximone as emergency medication for life threatening asthma and suppression of allergic airway inflammation as measured in a house dust mite asthma model

Rationale: Enoximone is a phosphodiesterase 3 inhibitor and prevents hydrolysis of cAMP. effects. Enoximone was designed to treat heart failure, accomplished by increasing myocardial contractility while inducing simutaneously vasodilatation. Smooth muscle relaxation also occurs in the airways. Surprisingly reduced pulmonary inflammation is observed in enoximone treated patients. Here we report the use of enoximone in status asthmaticus patients and show the results of enoximone administration in a dust mite murine asthma model. Patient reports: 8 Patients with status asthmaticus were presented in a refractory emergency situation and received enoximone. Bronchodilation was immediate without side-effects. Study methods: C57bl/6 mice were either sensitized with 10 mcg of house dust mite (HDM) or received PBS as a control, followed by 5 daily challenges with HDM 10 mcg 10-15 days after sensitization. Therapeutic intervention with enoximone was performed with enoximone before sensitisation and challenge with HDM. Conclusions: Enoximone is a valuable addition to the treatment of status asthmaticus. Severe bronchoconstriction hinders inhalational medication; I.V. administration of enoximone overcomes this problem, without the side effects seen with e.g. catecholamines. Therapeutic intervention of PDE3 activity by enoximone is an interesting new therapy of an 9old9 heart failure drug in asthma and may open a wider field for implementation in ER treatment, IC treatment and peri-operative treatment. Additional research to discover the underlying mechanism of action is being prepared.