PH_I_P: Pharmaceutical Sciences I. Posters
Noémi Papp1, Szabolcs Koncz1, György Bagdy1,2,3
1 Department of Pharmacodynamics, Semmelweis University, Budapest,
2 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest
3 NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest
Introduction: Tolperisone (TOL) is an efficient and well-tolerated centrally acting muscle relaxant used for the treatment of spasticity and acute muscle spasms. It inhibits voltage-gated sodium and calcium channels, yet the exact mechanism of action is not fully understood. Its potential use in additional indications, such as neuropathic pain and fibromyalgia, has been suggested. Pregabalin (PRE), a calcium channel inhibitor, is an anticonvulsant and anxiolytic drug used to treat, among others, neuropathic pain and fibromyalgia. Pain and sleep disturbances are closely associated, therefore, it is essential to evaluate the sleep effects of drugs applied in these disorders. Whereas PRE is known to alter sleep, namely, it causes somnolence as a common side effect in addition to alterations of several sleep parameters, TOL is assumed to be less sedative, although preclinical studies are lacking.
Aim: Our aim was to examine the effects of TOL on the sleep-wake architecture in rats, and to reveal differences from those of PRE.
Methods: After recovery from electroencephalographic (EEG) electrode implantation surgery, male Wistar rats (n = 15) were treated intraperitoneally with (a) 15 mg/kg TOL and vehicle, or (b) 15 mg/kg PRE and vehicle, at the beginning of their passive phase. Frontoparietal EEG was recorded and scored for 6 h after treatments. Time spent in wakefulness (W), rapid eye movement sleep (REMS), and non-REMS (NREMS) were calculated for the summarized 6 h.
Results: PRE caused alterations in all the three vigilance stages: it elevated the time spent in NREMS (p<0.0001), while reduced the time spent in W (p<0.01) as well as REMS (p<0.01). In contrast, TOL did not affect the time spent in any of the vigilance stages.
Conclusion: Whereas the sleep-wake architecture was markedly altered by PRE, it remained undisturbed following TOL administration. These data confirm the lack of sleep-disrupting side effect of TOL that might be beneficial in patients both with and without sleep problems.
Funding: This study was supported by the 2018-1.3.1-VKE-2018-00030 Competitiveness and excellence cooperations project provided by the National Research, Development and Innovation Fund, and by the ÚNKP-20-4-I-SE-6 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.
Semmelweis University, Doctoral School of Pharmaceutical Sciences