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Co-treatment with rivastigmine and idalopirdine reduces the propensity for falls in a rat model of falls in Parkinson’s disease

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A Correction to this article was published on 25 October 2019

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Abstract

Rationale

Falls in patients with Parkinson’s disease (PD) are associated with cognitive, specifically attentional impairments and with losses in cholinergic projection systems. We previously established an animal model of the combined basal forebrain cholinergic—striatal dopaminergic losses of PD fallers (Dual Lesioned, DL, rats) and demonstrated that treating DL rats with an acetylcholinesterase inhibitor (AChEI), donepezil, together with a 5HT6 receptor antagonist, idalopirdine, reduced fall frequency and improved associated aspects of the performance of DL rats traversing rotating rods.

Objectives

Here, we employed a longer and more taxing rotating beam apparatus to determine the potential therapeutic efficacy of idalopirdine when combined with the pseudo-irreversible, and thus relatively long-acting, AChE- and butyrylcholinesterase- (BuChE) inhibitor rivastigmine.

Results

As before, vehicle-treated DL rats fell more frequently, committed more slips, and exhibited more movement stoppages than intact control rats. Repeated intermittent administration of rivastigmine and idalopirdine significantly improved the performance of DL rats. Rivastigmine alone also produced strong trends for reducing falls and slips. The combination treatment was more effective than rivastigmine alone in reducing stoppages and stoppage-associated falls. As before, idalopirdine treatment alone was ineffective.

Conclusions

These results extend the prediction that the combined treatment with idalopirdine and an AChEI improves complex movement control and reduces the propensity for falls in patients with movement disorders. Because of the importance of finding better treatments for gait and balance deficits in PD, the present results may further motivate a clinical exploration of the usefulness of this combination treatment.

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Change history

  • 25 October 2019

    After publication of this paper, the authors determined that the “Acknowledgments” section was omitted. Below is the “Acknowledgments” statement.

  • 25 October 2019

    After publication of this paper, the authors determined that the ���Acknowledgments��� section was omitted. Below is the ���Acknowledgments��� statement.

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Correspondence to Martin Sarter.

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The research described in this manuscript was supported by a grant from H. Lundbeck A/S, Valby (Denmark) to M.S. I.d.J. is an employee of H. Lundbeck.

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Koshy Cherian, A., Kucinski, A., Wu, R. et al. Co-treatment with rivastigmine and idalopirdine reduces the propensity for falls in a rat model of falls in Parkinson’s disease. Psychopharmacology 236, 1701–1715 (2019). https://doi.org/10.1007/s00213-018-5150-y

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