Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception

• Published in: Psychopharmacology 2020-05, Vol.237 (5), p.1435-1446
• Main Authors: Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica
• Format: Article
• Language: English
• Subjects: Acetic acid; Analgesics; Analysis; Antiepileptic agents; Biomedical and Life Sciences; Biomedicine; Care and treatment; Drug dosages; Drug interaction; Formaldehyde; Headache; Inflammation; Metoclopramide; Migraine; Naproxen; Neurosciences; Nonsteroidal anti-inflammatory drugs; Oral administration; Original Investigation; Pain; Pain perception; Paracetamol; Pharmacology/Toxicology; Propyphenazone; Psychiatry
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-020-05470-7

Rationale Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.