The effects of Vilazodone, YL-0919 and Vortioxetine in hemiparkinsonian rats

Smith, Samantha K.; Sergio, Jordan; Coyle, Michael; Elder, Kayla; Centner, Ashley; Cohen, Sophie; Terry, Michelle; Lipari, Natalie; Glinski, John; Wheelis, Emily; Budrow, Carla; Bishop, Christopher

doi:10.1007/s00213-022-06078-9

Cited by 4 publications

(6 citation statements)

References 109 publications

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“…Post hoc analyses revealed that ALO AIMs were elevated within a week of starting treatment compared to Day 1 and were maintained when tested a week later (both p < 0.05). When analyzing the effects of daily L-DOPA on ALO AIMs in Experiment 2, the same pattern of effects was observed (χ 2 (2) = 17.543, p < 0.05), supporting prior work that within 1 week of daily treatment, AIMs stabilize at this dose of L-DOPA [ 35 , 36 , 42 ].…”

Section: Resultssupporting

confidence: 82%

“…This has led to efforts to combine these known anti-dyskinetic 5-HT actions by using multimodal 5-HT compounds, first developed for their anti-depressant actions. Recently, we confirmed the potential of dual-action 5-HT 1A/1B R agonists and SERT blockers vilazodone (VZD) and vortioxetine (VTX) to dose-dependently attenuate LID [ 35 ]. The durability of this multimodal mechanism of action was demonstrated following chronic treatment with VZD, which sustained anti-dyskinetic efficacy while maintaining the motor benefits of L-DOPA [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 83%

“…Recently, we confirmed the potential of dual-action 5-HT 1A/1B R agonists and SERT blockers vilazodone (VZD) and vortioxetine (VTX) to dose-dependently attenuate LID [ 35 ]. The durability of this multimodal mechanism of action was demonstrated following chronic treatment with VZD, which sustained anti-dyskinetic efficacy while maintaining the motor benefits of L-DOPA [ 35 , 36 , 37 ]. Therefore, to further support the promise of such broader acting compounds, here, we used hemiparkinsonian rats to better characterize VTX.…”

Section: Introductionmentioning

confidence: 83%

“…In recent years, in attempts to overcome prior limitations, several novel strategies have been pursued, including biased and selective 5-HT 1A R agonists [ 45 , 46 ], combination strategies [ 42 , 47 ], and multimodal 5-HT approaches [ 35 , 36 , 48 ]. With several studies now supporting a combined SERT blockade and 5-HT 1 R agonism as a promising profile, we sought to characterize the durability and pharmacology of the FDA-approved multimodal 5-HT antidepressant VTX in the hemiparkinsonian rodent.…”

Section: Discussionmentioning

confidence: 99%

“…Following the confirmation of stable dyskinesia, rats who met inclusion criteria (n = 35) later received acute or chronic injections of vortioxetine hydrobromide (VTX; Sigma-Aldrich) at a dose of 0, 3, or 10 mg/kg (s.c.) in a vehicle comprised of 25% dimethyl sulfoxide (DMSO; VWR International; Randor, PA, USA). Doses were chosen based on effective doses revealed in prior investigation [ 35 ]. All drugs were administered at 1 mL/kg.…”

Section: Methodsmentioning

confidence: 99%

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Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia

Budrow

Elder

Coyle

et al. 2023

Cells

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Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms that result from loss of nigrostriatal dopamine (DA) cells. While L-DOPA provides symptom alleviation, its chronic use often results in the development of L-DOPA-induced dyskinesia (LID). Evidence suggests that neuroplasticity within the serotonin (5-HT) system contributes to LID onset, persistence, and severity. This has been supported by research showing 5-HT compounds targeting 5-HT1A/1B receptors and/or the 5-HT transporter (SERT) can reduce LID. Recently, vortioxetine, a multimodal 5-HT compound developed for depression, demonstrated acute anti-dyskinetic effects. However, the durability and underlying pharmacology of vortioxetine’s anti-dyskinetic actions have yet to be delineated. To address these gaps, we used hemiparkinsonian rats in Experiment 1, examining the effects of sub-chronic vortioxetine on established LID and motor performance. In Experiment 2, we applied the 5-HT1A antagonist WAY-100635 or 5-HT1B antagonist SB-224289 in conjunction with L-DOPA and vortioxetine to determine the contributions of each receptor to vortioxetine’s effects. The results revealed that vortioxetine consistently and dose-dependently attenuated LID while independently, 5-HT1A and 5-HT1B receptors each partially reversed vortioxetine’s effects. Such findings further support the promise of pharmacological strategies, such as vortioxetine, and indicate that broad 5-HT actions may provide durable responses without significant side effects.

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Section: Resultssupporting

confidence: 82%