PhD Scientific Days 2024

Pharmaceutical Sciences and Health Technologies I.

Sleep-wake Architecture and qEEG of Tolperisone and Pregabalin: Acute and Long-term Effects

Text of the abstract

Introduction
Neuropathic pain affects nearly 10% of the society and is often associated with insomnia and poor sleep quality. According to recent research, tolperisone can be effective for neuropathic pain with a more favorable side effect profile than a first-line treatment, pregabalin. Pregabalin has been shown to have sedative side effects. This may be beneficial in the short term for pain related insomnia, but it may cause fatigue in patients later, during the daytime.

Aims
The aim of our study was to compare the 23-hour effects of different single doses of tolperisone and pregabalin on sleep-wake architecture and quantitative EEG (qEEG).

Methods
Male Wistar rats were equipped with electroencephalography (EEG) and neck muscle electrodes. After the regeneration period, intraperitoneal tolperisone or pregabalin injection (5, 15 or 45 mg/kg) or vehicle were administered at the beginning of the passive phase. After injection EEG, EMG and motility of the animals were registered for 23 hours.

Result
The results showed that 15 and 45 mg/kg pregabalin dose-dependently increased non-rapid eye movement (NREM) sleep time and decreased rapid-eye movement sleep time. The 45 mg/kg dose even increased qEEG delta power during wakefulness and NREM sleep. In contrast, neither doses of tolperisone, nor 5 mg/kg pregabalin had any effects on sleep-wake architecture or qEEG delta power in the registered 23 hours.

Conclusion
The long-term sedative effects observed during the next active period of the animals indicate that after taking high doses of pregabalin in the evening, patients might experience drowsiness the next day. The dose-dependent disturbance of REM sleep time of pregabalin suggests that tolperisone might be an ideal alternative to pregabalin with more favorable side effects regarding sleep quality.

Funding:
Grant: 2017-1.2.1-NKP-2017-00002, NAP2022-I-4/2022, 2020-4.1.1.-TKP2020, TKP2021-EGA-25, 2018-1.3.1-VKE-2018-00030
The contribution of Dóra Pothorszki was supported by the ÚNKP-23-3-I-SE-43 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund.
The publication was prepared also with the support of the Richter Gedeon Talentum Foundation established by Richter Gedeon Plc. in concordance with the framework of the Richter Gedeon PhD Scholarship.