University of SzegedOpportunity Contact
Enikő Koppány, Business Development Manager
Szeged, Hungary

University of Szeged Website

The application of desethamiodarone (DEA) in the treatment of arrhythmias would be more effective than chronic amiodarone (AMIO) treatment with better pharmacokinetics and with fewer adverse effects and with reduced unexpected drug interactions in humans.

Cardiovascular diseases including sudden cardiac death and stroke are among the leading causes of mortality in industrialized countries. At present the pharmacological treatment of arrhythmias including atrial fibrillation is not satisfactory since the available drugs either do not control arrhythmias properly or induce serious side effects, Therefore, there is an increasing demand for safe and effective new drugs to treat atrial fibrillation and arrhythmias. Chronic AMIO application is the most effective pharmacological treatment to combat atrial fibrillation and arrhythmias with less proarrhythmic risk than other currently used antiarrhythmics. However, AMIO – which has a very complex model of action inhibiting cardiac sodium, calcium, potassium currents, and beta-adrenoceptors – also exerts serious extracardiac adverse effects which generally limit its clinical use.

Description of Technology
During chronic AMIO treatment an active amiodarone metabolite, DEA appears in the plasma and tissues including the heart. Since both AMIO and DEA contain iodine it is proven that they inhibit and interfere with cardiac thyroid receptors and exert their antiarrhythmic effect partly by this mechanism. It was reported earlier that DEA binds to cardiac thyroid receptors with higher affinity. In summary, it is expected that chronic DEA treatment would be more effective than chronic AMIO treatment with better pharmacokinetics and with fewer adverse effects and with reduced unexpected drug interactions in humans.

DEA has in vivo and ex vivo antiarrhythmic effects comparable in strength to those of its parent compound AMIO in coronary occlusion induced ventricular arrhythmias in rats and guinea pigs and in tachypace induced atrial fibrillation in dogs and rabbits.

The cellular electrophysiological mechanisms of DEA were studied and compared to AMIO on cardiac action potentials in tissue preparations by applying the conventional microelectrode technique. The underlying transmembrane currents were studied in single isolated myocytes applying the patch-clamp technique. The measured cellular electrophysiological effects of DEA and AMIO were similar and comparable. These effects were achieved with lower blood and tissue levels of DEA comparing to those of AMIO, since DEA blood and tissue (heart, lung, liver and kidney) levels yielded significantly more drug accumulation with AMIO comparing it with DEA, after chronic per os 25-50 mg/Kg/day DEA and AMIO treatments.

The in vivo pharmacokinetic properties of DEA in dogs were favourable than those of AMIO, characterized by DEA having higher bioavailability (67.4 %) and a larger volume of distribution ( 34.9 L/Kg ) than those of AMIO (35.9 %) and (4.4 L/KG).

The 3 months chronic oral toxicity study in dogs showed no particular alteration in the major organs with DEA and AMIO, only in the lungs signs of moderate fibrosis were observed which was less severe with DEA comparing it with AMIO. Blood chemistry showed no alteration with DEA but significant leukocytopenia was observed with AMIO. It was concluded that equal doses of DEA and AMIO administrations caused similar antiarrhythmic effects and cellular mechanisms but less drug accumulation in various organs with  DEA than with AMIO treatments. This also associated with favourable pharmacokinetics and less toxicity of DEA comparing it to its parent compound AMIO.


  • Preventive effect of cardiac arrhythmias
  • The synthesis of DEA in large amount has been solved
  • Lower doses needed
  • Minor side effects, fewer complications
  • Whereas DEA during the AMIO treatment is always present, the human pharmacological effects are already partially known and safety risk is reduced

Type of Business Relationship Sought
Out license, Partnership

Patent Information

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