A galantamine–curcumin hybrid lacks the depressant side effect of acetylcholinesterase inhibitors

Abstract

Acetylcholinesterase inhibitors (AChEIs) are drugs that enhance cholinergic neuro-transmission and are used for the treatment of Alzheimer’s disease and myasthenia gravis. Common AChEIs include rivastigmine, donepezil and galantamine (GAL), but they can cause side effects like nausea, vomiting, depression and bradycardia. A potential link exists between AChEIs and increased depression risk. Recently, we have discovered a hybrid compound (4b) combining GAL and curcumin (CCN), which shows improved anticholinesterase activity and neuroprotective effects. It could be developed as a potential multitarget agent for neurodegenerative disorders. Here, we examine the compound’s depressant side effect on mice, comparing it to GAL and CCN. Tests were conducted twice using the tail suspension test (TST) and the forced swim test over an 8-day treatment period. The results showed that 4b lacked the depressant effect of GAL and even displayed a mild antidepressant effect similar to CCN in TST. This suggests that incorporating antidepressant fragments, like CCN, into AChEIs can potentially neutralize their depressive side effects.

Keywords:

• Galantamine
• curcumin
• fluoxetine
• acetylcholinesterase inhibitors
• tail suspension test
• forced swim test

Author contributions

Conceptualization, I.K. and I.D.; methodology, I.K.; investigation, I.K., M.A., G.S., I.P. and I.D.; writing—original draft preparation, I.D.; writing—review and editing, I.K., M.A., G.S., I.P. and I.D.; visualization, I.K.; supervision, I.D.; project administration, I.D.; funding acquisition, I.D. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the Science and Education for Smart Growth Operational Program and co-financed by the European Union through the European Structural and Investment funds (Grant No. BG05M2OP001-1.001-0003). The APC was funded by the Bulgarian National Roadmap for Research Infrastructure (Grant No. D01-271/2019).