Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated.
Nikola Tatalović, Teodora Vidonja Uzelac, Zorana Oreščanin-dušić, Aleksandra Nikolić-kokić, Mara Bresjanac, Duško Blagojević
Antioxidants (Basel, Switzerland) November 9, 2021 DOI: 10.3390/antiox10111792 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Isolated rat uterus |
| Interventions | Ibogaine propranolol glibenclamide |
| Dose | 10 mg/L (28.8 μmol/L) |
| Duration | 4 hours |
| Topics | Ibogaine |
| Keywords | Katp channels Antioxidative enzymes Catalase Contractility Glibenclamide Propranolol Superoxide dismutase Β-adrenergic receptors Ibogaine pharmacology ibogaine Uterine physiology uterus |
| Citations | 5 |
| Key findings | Ibogaine's pro-antioxidant effectiveness in rat uterus is mediated by β-adrenergic receptors and KATP channels. |
Abstract
Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since the role of KATP channels and β-adrenoceptors in ROS cellular circuit was established here we explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e., 28.8 μmol/L) was applied to isolated rat uterus (spontaneous and Ca2+-stimulated) and contractility and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and frequency of spontaneous active uteri immediately after addition that was prevented by propranolol (β1 and β2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor; only frequency) pre-treatment. In Ca2+-stimulated uteri, ibogaine decreased both amplitude and frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering, while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in SOD1 and an increase in CAT activity after 2 h. In Ca2+-stimulated uterus, there was also a decrease of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β-adrenergic receptors and KATP channels mediated.
Comparable studies
Other experimental studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. In vitro (SERT) | 2007 | Laboratory study | |
| Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. | 1992 | Laboratory study | |
| The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. | 2012 | Experimental study | |
| Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. | 1995 | Experimental study | |
| Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. | 1995 | Laboratory study |
Citations in the library
Cited by 2
Cites 16
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- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- How toxic is ibogaine? Clinical Toxicology 2016
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