Douleurs neuropathiques - page 3 - Publications Scientifiques

Dernière publication 01/05/2026

Activity of Nonhallucinogenic Ibogalogs on Chemotherapy-Induced Peripheral Neuro

In this study, we examined the effects of ibogaminalog (DM506), a nonhallucinogenic analog of ibogamine, in a mouse model of chemotherapy-induced...

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    [title] => Activity of Nonhallucinogenic Ibogalogs on Chemotherapy-Induced Peripheral Neuro
    [paragraph] => Activity of Nonhallucinogenic Ibogalogs on Chemotherapy-Induced Peripheral Neuropathic Pain in Mice | ACS Chemical Neuroscience
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Authors
Jason  Younkin, Eda  Koseli, Belle  Buzzi, Edward  Choi, Torin  Honaker, Randall L.  Davis, Dina  Manetti, Maria Novella  Romanelli, Aysel  Cetinkaya-Fisgin, Hugo R.  Arias, Ahmet  Hoke, Javier  Gonzalez-Maeso, M. Imad  Damaj

Lab
Journal
ACS Chemical Neuroscience
Abstract
In this study, we examined the effects of ibogaminalog (DM506), a nonhallucinogenic analog of ibogamine, in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) induced by paclitaxel. We also assessed the effects of tabernanthalog (TBG) and investigated the potential role of serotonin receptor subtype 2A (5-HT2AR) for both compounds. DM506 and TBG demonstrated antinociceptive activity in the CIPN model. DM506 produced a more prolonged effect, lasting between 10 and 14 days, with nociception reduction in mechanical (von Frey) and cold (acetone) hypersensitivity assays. These effects were observed in a dose- and time-dependent manner. Unlike some previous studies that reported effects lasting only hours, the effects we observed persisted for several days. Furthermore, neither compound produced long-lasting effects on locomotor activity, even at relatively high doses. The antinociceptive effects of both compounds in the CIPN mouse model were blocked by the 5-HT2AR selective antagonist volinanserin.In vitrostudies revealed that DM506 does not block cytokine/chemokine expression in microglial cells but partially protected dorsal root ganglion (DRG) neurons treated with paclitaxel in the 100–300 nM concentration range in a volinanserin-sensitive manner. We conclude that DM506 and TBG possess antinociceptive properties in mice via pathways involving 5-HT2AR activation. Although it is unlikely that this effect involves anti-inflammatory activity in microglia, partial neuroprotective activity in DRG neurons can be considered.
Keywords/Topics
ibogalogs; chronic pain; neuropathy; 5-HT2AR; mice; chemotherapy
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