Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine

Summary

Low-dose ketamine shows promise in reducing involuntary movements common in Parkinson's. A study explored how two common statins interact with ketamine's benefits in a preclinical model. Ketamine significantly lessened abnormal movements. While one statin unfortunately blocked these long-term positive effects, another statin, lovastatin, did not interfere, preserving ketamine's beneficial action. This reveals important drug interactions and supports ketamine's ongoing evaluation for Parkinson's-related movement issues.

Abstract

Sub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson’s disease case reports. In this study, we examined the effects on L-DOPA-induced dyskinesia of two statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard preclinical LID model. Sub-anesthetic ketamine attenuated the development of AIMs, while lovastatin only showed anti-dyskinetic activity at the beginning of the priming but did not prevent the development of LID. The polar pravastatin blocked the long-term anti-dyskinetic effects of ketamine, while the non-polar lovastatin did not. This study shows different classes of statins affect LID differentially, points to an important drug interaction and further supports ongoing clinical testing of sub-anesthetic ketamine to treat LID in individuals with Parkinson’s disease.

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