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Acanthamoeba spp. has recently been reported to express diverse group of ion-channels and receptors that are expressed by human cells which bind drugs that are used in non-infectious diseases. Bioinformatics computational tools, growth assays and 3D structural modeling has enabled the discovery of primitive muscarinic receptors, voltage gated calcium channels and transport pumps like Na-K ATPase in this protist pathogen. The significance of the reported receptors and ion-channels in the biology of Acanthamoeba is yet to be discovered. We selected Promethazine which is a known antagonist of proteins like dopaminergic, histaminergic, muscarinic receptors and calmodulin to determine its effects on the growth and proliferation of trophozoites and cysts of Acanthamoeba spp. In order to elucidate the receptors involved in the effects produced by promethazine, we also performed individual experiments on Acanthamoeba trophozoites and cysts in the presence of the agonist of the above-mentioned receptors. Our results show that promethazine in a range of 60-100µg/ml proved to be amoebicidal for Acanthamoeba trophozoites and at slightly higher doses 125-250 µg/ml also showed partial cysticidal effects. We also show the evidence of homology between the human targets of promethazine and similar targets in Acanthamoeba by the use of bioinformatic computational tools and 3D modeling. Promethazine and its structural analogs, because of being FDA approved and having a wider margin of safety that can be tested as potential anti-Acanthamoeba agents in diseases like keratitis and encephalitis caused by this protist pathogen.
This article was published in the following journal.
Name: ACS chemical neuroscience
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Specific effects of drugs and substances on metabolic pathways such as those occurring through the CYTOCHROME P-450 ENZYME SYSTEM. These include effects that often result in DRUG INTERACTIONS; FOOD-DRUG INTERACTIONS; and HERB-DRUG INTERACTIONS.
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.
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Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
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Immunoassay - ELISA
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