Produced by a parasitic fungus, Claviceps purpurea, the ergot alkaloid ergotamine is utilized in controlled concentrations pharmaceutically to treat postpartum hemorrhage and migraines. If uncontrolled, ergot alkaloids can produce gangrene, convulsions, and hallucinations, a phenomenon called ergotism. Ergot alkaloids also have a history of being used medicinally as early as the sixteenth century by midwives to accelerate childbirth or initiate abortion. By the nineteenth century, ergot alkaloids were used to treat hemorrhaging in childbirth which has been linked to increased occurrences of maternal mortalities in developing countries today. Ergot alkaloids have recently  been researched and used to treat neurological disorders, such as Parkinson’s disease. 

The effects of ergotamine are seen to impact blood pressure, heart rate, and dysfunction of thermoregulation. In vitro studies have revealed ergot mycotoxins' impact on the contraction responses of veins and arteries. Studies show that ergot alkaloids primarily act as partial agonists or antagonists on neurotransmitter receptor sites including dopamine, serotonin, and epinephrine. Inhibition of an essential enzyme, sodium-potassium ATPase, for maintenance of neuronal membrane potentials, has also been observed. Although there is a growing body of research today surrounding fungal-derived treatments, the mechanism of action of ergot alkaloid mycotoxins within the brain is still not well understood.

A recent study assessed the effects of ergotamine on the brain using the metabolic profile of mice to pinpoint pathways disturbed by fungus-derived pharmaceuticals. Results of the study showed the brainstem and cerebral cortex were significantly impacted by ergotamine. Dysregulation of epinephrine in the brainstem and 2-arachidonylglycerol, a psychoactive compound, was seen. The energy metabolites isobutyryl-L-carnitine and S-3-oxodecanoyl cysteamine and increased metabolites of adenylosuccinate were also observed within the cerebral cortex. Ergotamine’s influence on the cerebral cortex was suggested to lead to behavioral manifestations and motor incoordination. This study done in 2021 by Reddy et al. was the first to identify key metabolic pathways in the brain that cause the behavioral and physiological effects of ergot alkaloids in animals.

Sources:

Reddy, P., et al. (2021). Effects of ergotamine on the central nervous system using untargeted metabolomics analysis in a mouse model. Scientific reports.