Coronaridine congeners potentiate GABAA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner

(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission

“…The doses have been chosen based on previous studies showing antidepressant-like activity of (-)-ibogaine and noribogaine (Rodrıguez,Urbanavicius, 2020), and a lack of sedative activity of (+)-catharanthine. Note that animals receiving (+)-catharanthine (Arias,Do Rego, 2020a) or (-)-18-MC, at doses of 20 or 40 mg/kg, showed locomotor activity, assessed 1 hour after their administration, similar to that observed in untreated animals, thus ruling out a possible impact of the locomotor effects of these compounds at the different doses used in the behavioral tests conducted in this study.…”

“…Plant alkaloids such as (-)-ibogaine [and its main metabolite noribogaine (12-hydroxyibogamine)] and (+)-catharanthine, and the synthetic derivative 18-methoxycoronaridine (18-MC) are coronaridine congeners with very interesting behavioral profile, including anti-addictive (Carnicella et al, 2010;Glick et al, 1999;Glick et al, 1991;Luz,Mash, 2021;Maisonneuve,Glick, 2003), sedative (Arias et al, 2020a), and antinociceptive (Arias et al, 2020b) activities.…”

Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors

“…Ibogaine has been extensively studied for anti-addictive properties, but clinical trials failed due to cardiotoxicity [ 68 ]. Additionally, ibogain-type alkaloids like catharanthine and coronaridine congeners have been found to selectively inhibit the nAChRs and Cav2.2 channels, and to potentiate GABA A receptors [ 69 , 70 , 71 , 72 ]. Ibogaine and coronaridine are NMDA receptor antagonists, with K i = 1.1 µM and K i = 6.2 µM, respectively [ 73 ].…”

Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels

“…The number of counts in oxaliplatin + congener-treated mice were similar to that observed in vehicle + vehicle-treated animals, suggesting that coronaridine congeners do not produce per se any further effect on mouse spontaneous mobility. Since (+)-catharanthine (63 mg/kg) decreased mouse locomotor activity due to its sedative effect (Arias et al, 2020), additional tests to determine the effect of coronaridine congeners on spontaneous mobility and exploratory activity cannot be accomplished.…”

“…In general, coronaridine congeners (e.g., ( ± )-18-methoxycoronaridine [( ± )-18-MC] alleviate drug craving and decrease relapse in humans and diminish drug self-administration in animals (Maisonneuve and Glick, 2003). Although preliminary results suggest that ( ± )-18-MC has antidepressant, anxiolytic and anti-obesity activities (Maisonneuve and Glick, 2003;Taraschenko et al, 2008), and (+)-cantharanthine has sedative activity (Arias et al, 2020), there is no study demonstrating its potential anti-pain (i.e., analgesic) activity. In this regard, the primary objective of this study was to determine the anti-neuropathic pain activity of ( ± )-18-MC and (+)-catharanthine in mice by using the oxaliplatin-induced neuropathic pain paradigm and cold plate test (Cavaletti et al, 2001).…”