@article{ebbc2c87c16b4e6c974cbb0e4d1ba3e9,
title = "Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels",
abstract = "The primary aim of this study was to determine the anti-neuropathic activity of (±)-18-methoxycoronaridine [(±)-18-MC] and (+)-catharanthine in mice by using the oxaliplatin-induced neuropathic pain paradigm and cold plate test. The results showed that both coronaridine congeners induce anti-neuropathic pain activity at a dose of 72 mg/kg (per os), whereas a lower dose (36 mg/kg) of (+)-catharanthine decreased the progress of oxaliplatin-induced neuropathic pain. To determine the underlying molecular mechanism, electrophysiological recordings were performed on α9α10, α3β4, and α4β2 nAChRs as well as voltage-gated calcium (CaV2.2) channels modulated by G protein-coupled γ-aminobutyric acid type B receptors (GABABRs). The results showed that (±)-18-MC and (+)-catharanthine competitively inhibit α9α10 nAChRs with potencies higher than that at α3β4 and α4β2 nAChRs and directly block CaV2.2 channels without activating GABABRs. Considering the potency of the coronaridine congeners at Cav2.2 channels and α9α10 nAChRs, and the calculated brain concentration of (+)-catharanthine, it is plausible that the observed anti-neuropathic pain effects are mediated by peripheral and central mechanisms involving the inhibition of α9α10 nAChRs and/or CaV2.2 channels.",
keywords = "(+)-catharanthine, 18-Methoxycoronaridine, Coronaridine congeners, Neuropathic pain, Nicotinic acetylcholine receptors, Voltage-gated (Ca2.2) calcium channels",
author = "Arias, {Hugo R.} and Tae, {Han Shen} and Laura Micheli and Arsalan Yousuf and Carla Ghelardini and Adams, {David J.} and {Di Cesare Mannelli}, Lorenzo",
note = "Funding Information: This work was supported by grants from the Italian Ministry of Instruction, University and Research ( MIUR ) and the University of Florence (to C.G.), Australian Research Council (Discovery Project Grant DP150103990 to D.J.A.), and Oklahoma State University Center for Health Sciences (to H.R.A.). The authors thank to Dr. Kuehne (University of Vermont, VT, USA) for the (+)-catharanthine hydrochloride, Prof. A. Nicke (Ludwig Maximilian University of Munich) and Prof. M. Chebib (University of Sydney) for the plasmids, and Dr. M. Ortells (University of Moron, Argentina) for the calculation of the logBBB value for (+)-catharanthine. Funding Information: This work was supported by grants from the Italian Ministry of Instruction, University and Research (MIUR) and the University of Florence (to C.G.), Australian Research Council (Discovery Project Grant DP150103990 to D.J.A.), and Oklahoma State University Center for Health Sciences (to H.R.A.). The authors thank to Dr. Kuehne (University of Vermont, VT, USA) for the (+)-catharanthine hydrochloride, Prof. A. Nicke (Ludwig Maximilian University of Munich) and Prof. M. Chebib (University of Sydney) for the plasmids, and Dr. M. Ortells (University of Moron, Argentina) for the calculation of the logBBB value for (+)-catharanthine. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = sep,
day = "15",
doi = "10.1016/j.neuropharm.2020.108194",
language = "English",
volume = "175",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Ltd",
}