IRLAB’s drug mesdopetam has displayed antipsychotic properties in an advanced model of Parkinson’ s disease psychosis (PD-P).
Published in Neurotherapeutics, a series of preclinical studies have shown that mesdopetam displays key features associated with antipsychotic efficacy in this PD-P model.
The research was carried out in collaboration with the group for Integrative Neurophysiology, Lund University, Sweden.
The team have suggested that mesdopetam should be further explored as a potential novel treatment option for psychosis in Parkinson’s disease.
Nicholas Waters, EVP & Head of R&D at IRLAB, stated: “The brain state characterisation presented in the paper is an impressive new technique which enables a new level of understanding of the brain mechanisms underlying PD-P and provides a great tool for evaluation of potential new therapies.
“These new results strongly support that mesdopetam has potential as a novel therapeutic in PD-P, also in light of the excellent safety and tolerability profile seen in clinical studies with mesdopetam.”
Preclinical studies
Parkinson’s psychosis is characterised by hallucinations and paranoid delusion, and is experienced by 20 to 40% of people with the condition.
The team’s studies are based on characterisation of the neurophysiological brain state in an advanced preclinical model of PD-P.
The effects of Mesdopetam, along with two compounds, clozapine and pimavanserin, which are clinically used to alleviate PD-P, and an experimental D3 antagonist, were investigated.
The studies revealed that the three compounds could reverse important features associated with the psychosis like state, including a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronisation between different brain regions. These results suggest the drug has antipsychotic properties.
Additionally, an overall comparison including clozapine, pimavanserin, and the experimental dopamine D3 receptor antagonist SB277011-A, indicated that mesdopetam was more similar to SB277011-A, than to the other compounds.
The findings support that the dopamine D3 receptor plays a role in PD-P and further corroborates that dopamine D3 receptor antagonism is an important mechanism of action underlying the pharmacological effects of mesdopetam.
The authors write: “In conclusion, our results indicate that mesdopetam shares certain key treatment effects with existing antipsychotic treatments for PD-P and consequently may have the potential to become a novel antipsychotic treatment option in this condition.
“At the same time, the specific response patterns of the different drugs could help elucidate their respective mechanisms of action and help predict potential side effects.
“In a broader perspective, studies linking the effects of pharmacological treatments on neurophysiological brain states to neurochemical properties as well as behavioural data, has the potential not only to speed up drug development but also to fill a significant knowledge gap in neuroscience by helping to merge the disparate descriptions of brain functions that have emerged from the different scientific traditions of neurochemical and neurophysiological studies.”
