Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B

Lolitrem B is an indole diterpenoid toxin found in perennial ryegrass. Although lolitrem B confers beneficial effects to the plant, these are counteracted by adverse effects observed animals that ingest it which can result in behavioural changes, ataxia and tremor and, in the most severe cases, seizures and death (Tor-Agbidye et al 2001). Morbidity and mortality of livestock can be in significant numbers (Cunningham 1959, Combs et al, 2014). Currently no therapeutic treatment is available that can be delivered at a flock-wide level to mitigate the large-scale effects observed in animals during critical outbreaks. Platforms for drug testing have been difficult to establish due to seasonal variations in lolitrem B in pasture-based feeds and the difficulty in extracting this highly lipophilic toxin (Munday-Finch, 1997). To overcome this, a reproducible and reliable model of PRGT in sheep was established utilizing a feed containing high levels lolitrem B toxin. This model was compared to a rodent model where animals were exposed to pure lolitrem B toxin isolated from perennial ryegrass. Establishment of these model systems allowed a number of therapeutics to be trialled. The most significant improvements were observed in movement, behaviour and reduction of stress by administration of potassium bromide. Pharmaceutical products that could improve clinical outcomes, reduce mortality can now be tested using this experimental model. This study also shows that lolitrem B induces activation of stress pathways in the brain and identified a clear role for this toxin in for testing of pharmaceutics with anxiolytic activity.