Disclosures: Amy Halseth, PhD: Neurana Pharmaceuticals: Employment, Stockholder/Ownership Interest (excluding diversified mutual funds)

Objective: To explore the impact of tolperisone, a centrally-acting muscle relaxant being developed in the U.S. for treatment of acute painful muscle spasms, on sedation and cognitive function measures using driving simulation, compared to placebo and cyclobenzaprine

Design: 3-way, randomized, blinded, crossover study

Setting: Inpatient research unit

Participants: 31 healthy volunteers

Interventions: 150 mg tolperisone TID, 10 mg cyclobenzaprine TID, and placebo TID for 3 days; 4-day washouts between randomized treatments.

Main Outcome Measures: Standard Deviation of Lateral Position (SDLP) on a 100 km (60 min) simulated driving test. The test was conducted on Day 1 one hour post-dose (acute effects around tolperisone Tmax), morning of Day 2 pre-dose (next day residual effects), and Day 3 one hour post-dose (effects with repeated dosing). CogScreen Symbol Digit Coding (SDC) and patient reported sleepiness (Karolinska Sleepiness Scale) were also measured.

Results: SDLP with tolperisone was similar to placebo, whereas cyclobenzaprine significantly increased SDLP (P<.01 vs placebo on all days). The increase in SDLP with cyclobenzaprine was greatest on Days 1 and 2, with 3× more cyclobenzaprine-treated than tolperisone-treated subjects having an increase of >4.4 cm, a pre-defined threshold for increased risk. Despite 58.6% of cyclobenzaprine subjects having a >4.4 cm increase in SDLP on Day 1, only 10.3% reported feeling unsafe to drive. Additional measures of driving performance were consistent with SDLP findings. Secondary measures confirmed the finding of non-sedation for tolperisone relative to placebo, with no significant differences in SDC or sleepiness.

Conclusions: Tolperisone 150 mg TID was found to be similar to placebo on measures of driving, self-reported sleepiness, and cognition, in contrast to cyclobenzaprine which showed impact on these measures. This suggests that tolperisone may have utility as a muscle relaxant, without sedation or impact on driving ability seen with other muscle relaxants.

Level of Evidence: Level I

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PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/novel-muscle-relaxant-tolperisone-showed-no-evidence-of-sedation-in-a-driving-simulation-study-while-cyclobenzaprine-increased-sedation/