Ponazuril (ACD-855)

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Ponazuril is a triazine-based antiprotozoal drug, primarily used in veterinary medicine to treat Sarcocystis neurona (the causative agent of Equine Protozoal Myeloencephalitis, EPM) and other coccidial infections. It is the active metabolite of toltrazuril and works by disrupting protozoal mitochondrial electron transport and folate metabolism.

While ponazuril is not FDA-approved for human use, its mechanism of action and effects on parasitic infections have led to some speculative and experimental off-label applications, particularly in neurology and psychiatry.

Recent pharmacological research suggests that ponazuril might possess some nootropic properties of their own. A project aimed at identification of small molecules with a stimulatory effect on BDNF and NGF as a direction explored in signaling in search for novel treatment options for Alzheimer’s disease, depression, possibly other psychiatric conditions and disorders characterized by cognitive impairment, found ponazuril to be a positive allosteric modulator of Trk receptors. It demonstrated pro-cognitive effects in various preclinical in vivo models in mice. Cognitive enhancement was also seen in age-related decline in memory. Furthermore, studies in rodents suggest that ponazuril might display anti-depressant-like effects, as evidenced by the forced swim test model.

Toxoplasmosis, caused by the Toxoplasma gondii parasite, is estimated to infect 30-50% of the world’s population. Its prevalence varies significantly by region, and while in the United States it is believed to occur in around 11%, in some European countries it can affect as much as 90% people. It has been linked to psychiatric disorders (schizophrenia, bipolar disorder) and neurodegenerative conditions. Ponazuril’s ability to cross the blood-brain barrier (BBB) makes it a candidate for mitigating chronic Toxoplasma – related neuroinflammation. Anecdotal reports suggest improvements in brain fog, fatigue, and cognitive dysfunction in patients with suspected chronic parasitic infections.

Toxoplasma gondii alters dopamine and GABA pathways in the brain. Some neurodivergent individuals (particularly those with autism or ADHD) exhibit immune dysregulation, chronic infections, or elevated Toxoplasma antibodies. In such cases, antiprotozoals might help if an underlying infection exacerbates symptoms. By eliminating the parasite, ponazuril might restore normal neurotransmission in affected individuals. No direct studies exist, however, on ponazuril’s neuromodulatory effects beyond antiprotozoal action. Anecdotal reports suggest some children with autism and confirmed parasitic infections show behavioral improvements after antiprotozoal treatment, but controlled studies are lacking.

Ponazuril’s safety profile in humans is not well-established, though related drugs (i.e., nitazoxanide) are generally well-tolerated.