Diminazene aceturate is a synthetic organic compound used as an anti-infective agent in veterinary medicine to combat microscopic parasites. As an aromatic diamidine, it is formulated as a water-soluble salt suitable for injectable solutions and is commonly recognized by its trade name, Berenil®.
Primary Veterinary Applications
Diminazene aceturate is used to treat and control protozoan diseases in domestic animals like cattle, horses, and dogs. One of its main applications is treating trypanosomiasis, a disease caused by Trypanosoma parasites. In African cattle, this condition is often called Nagana and is transmitted by the tsetse fly, leading to significant economic losses. The drug is effective against several species of these parasites that cause disease in livestock.
Another application is managing babesiosis, a tick-borne illness also known as redwater or tick fever. This disease is caused by Babesia parasites that infect and destroy red blood cells, causing fever, anemia, and hemoglobinuria, which is the presence of hemoglobin in the urine. The drug is valued for treating infections in cattle and dogs with a lower tendency for relapse. It has also shown activity against theileriosis, another tick-borne disease caused by Theileria parasites that threatens cattle.
Mechanism of Action
Diminazene aceturate eliminates parasites by binding directly to their deoxyribonucleic acid (DNA), showing a preference for regions rich in adenine-thymine base pairs. This binding is non-intercalative, attaching to the outside of the DNA structure in the minor groove. This interaction interferes with DNA replication and also inhibits the synthesis of proteins, which are necessary for virtually all cellular functions. By halting these processes, the drug prevents the parasite from multiplying, which leads to its death.
The drug’s action is selective, targeting the parasite’s kinetoplast DNA (kDNA), a network of circular DNA inside the mitochondria of protozoa like Trypanosoma. It also inhibits the mitochondrial type II topoisomerase enzyme in trypanosomes. This enzyme manages DNA structure during replication, and its inhibition provides another pathway to disrupt the parasite’s life cycle.
Administration and Potential Side Effects
A veterinarian administers diminazene aceturate through a deep intramuscular injection. The therapeutic dose is calculated based on the animal’s body weight, with a common recommendation being 3.5 milligrams of the drug per kilogram of body weight, given as a single dose. Accurate dosage calculation is necessary because the margin between a therapeutic and toxic dose is narrow. The drug is absorbed into the bloodstream, reaching peak levels within an hour.
Administration can lead to side effects. Common reactions are localized to the injection site, where animals may experience transient pain, inflammation, or swelling. More serious systemic effects can occur if the dosage is too high or the animal has a pre-existing sensitivity.
Severe toxicity can impact major organs. The drug is known to accumulate in the liver and kidneys, and residues can persist in these tissues for several weeks after treatment. Overdosing can cause toxic damage to these organs and the brain. Signs of toxicity include neurological symptoms like tremors, uncoordinated movements, and convulsions, requiring careful management by veterinary professionals.
Emerging Research and Other Potential Uses
Scientific research is exploring other therapeutic applications for diminazene aceturate, stemming from its discovery as an activator of angiotensin-converting enzyme 2 (ACE2). ACE2 is an enzyme on cell surfaces in organs like the lungs and heart that helps regulate blood pressure and inflammation. By activating ACE2, the compound can trigger biological effects separate from its anti-protozoal activity.
This ACE2-activating property has led to investigations into its potential for treating conditions involving inflammation and tissue damage. Studies have explored its use in models of pulmonary hypertension, a type of high blood pressure affecting lung arteries. Research has also examined its ability to mitigate lung injury and improve heart function following a myocardial infarction, suggesting potential anti-inflammatory and tissue-protective effects.
The compound’s connection to ACE2 has also prompted exploration into its effects on viral diseases, as some viruses use this receptor to enter host cells. These potential applications are purely experimental. The drug is not approved for these conditions in either humans or animals, and this research remains in the preclinical or laboratory stage.