Pregabalin–Tolperisone Combination to Treat Neuropathic Pain: Improved Analgesia and Reduced Side Effects in Rats

Autor: Nariman Essmat, Anna Rita Galambos, Péter P. Lakatos, Dávid Árpád Karádi, Amir Mohammadzadeh, Sarah Kadhim Abbood, Orsolya Geda, Rudolf Laufer, Kornél Király, Pál Riba, Zoltán S. Zádori, Éva Szökő, Tamás Tábi, Mahmoud Al-Khrasani
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceuticals, Vol 16, Iss 8, p 1115 (2023)
Druh dokumentu: article
ISSN: 1424-8247
DOI: 10.3390/ph16081115
Popis: The current treatment of neuropathic pain (NP) is unsatisfactory; therefore, effective novel agents or combination-based analgesic therapies are needed. Herein, oral tolperisone, pregabalin, and duloxetine were tested for their antinociceptive effect against rat partial sciatic nerve ligation (pSNL)-induced tactile allodynia described by a decrease in the paw withdrawal threshold (PWT) measured by a dynamic plantar aesthesiometer. On day 7 after the operation, PWTs were assessed at 60, 120, and 180 min post-treatment. Chronic treatment was continued for 2 weeks, and again, PWTs were measured on day 14 and 21. None of the test compounds produced an acute antiallodynic effect. In contrast, after chronic treatment, tolperisone and pregabalin alleviated allodynia. In other experiments, on day 14, the acute antiallodynic effect of the tolperisone/pregabalin or duloxetine combination was measured. As a novel finding, a single dose of the tolperisone/pregabalin combination could remarkably alleviate allodynia acutely. It also restored the neuropathy-induced elevated CSF glutamate content. Furthermore, the combination is devoid of adverse effects related to motor and gastrointestinal transit functions. Tolperisone and pregabalin target voltage-gated sodium and calcium channels, respectively. The dual blockade effect of the combination might explain its advantageous acute analgesic effect in the present work.
Databáze: Directory of Open Access Journals
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