Objective: This study evaluated potential anti-tremor properties of eslicarbazepine acetate (ESL), an antiseizure medication approved for treatment of focal-onset epilepsy, in the harmaline-induced tremor mouse model.

Background: Essential tremor (ET) is a common movement disorder, affecting up to 5% of individuals over 65. Its hallmark feature is an 8-12 Hz kinetic tremor of upper limbs, often accompanied by head and voice tremor. Current treatment relies primarily on pharmacological agents, yet almost 55% of patients respond inadequately.

Method: Quantitative electroencephalography (EEG) was recorded for 6 hours in freely moving mice (n=12), previously implanted with electrodes on motor cortex and cerebellum, under a cross-over design (drug conditions randomly administered; 2 administrations per week; 3-day interval). Tremor activity (n=12 per group) was assessed for 8 minutes, after a 10 minute habituation period, in a tremor monitor chamber. For both EEG and tremor activity experiments, animals received ESL (75 and 150 mg/kg, per gavage), propranolol (10-20 mg/kg, intraperitoneally) as reference, or vehicle, 20-30 min before harmaline (20 mg/kg, intraperitoneally).

Results: EEG: In vehicle-treated mice, harmaline induced a sustained low gamma band increase in both brain regions. Similarly to propranolol, ESL treatment significantly, and dose-dependently, prevented harmaline-induced low gamma oscillation increase compared to vehicle (ESL 75 mg/kg p<0.05 in motor cortex, ESL 150 mg/kg p<0.01 in both brain regions, at 2 hours after harmaline administration). Tremor activity: In vehicle-treated mice, harmaline induced a generalized tremor activity peaking at 12-14 Hz. ESL, similarly to propranolol, reduced the harmaline-induced tremor activity (-58,7% by ESL 75 mg/kg p = 0.006, -65,2% by ESL 150 mg/kg p = 0.001, vs vehicle) using the Tremor Index (TI) calculation. TI reflects the difference between the average energy within 10-16 Hz bandwidth (harmaline-induced tremor range) and the energy within 1-9 Hz (general motor activity), minimizing the confounding influence of locomotion, grooming or postural adjustments.

Conclusion: ESL reversed harmaline-induced EEG alterations and attenuated tremor activity in a mouse model of ET. This effect, possibly attributed to a T-type calcium channel inhibition, may suggest a therapeutic potential for this movement disorder.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/anti-tremorgenic-properties-of-eslicarbazepine-acetate-in-the-harmaline-induced-tremor-mouse-model/