Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis

•Leishmaniasis is a critical public health problem worldwide.•350 million people live in areas at risk, 14 million of them are affected and the number of reported and drug resistance cases is increasing.•There is no efficient vaccine and finding an alternative antileishmanial drug is essential.•Antileishmanial activity of amiodarone and dronedarone has recently been indicated.•Low cost and excellent pharmacokinetic properties make the amiodarone and dronedarone a promising alternative drug to the current treatments. Leishmaniasis is a group of human and animal diseases causing 20,000–40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment.