18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats.
S D Glick, M E Kuehne, I M Maisonneuve, U K Bandarage, H H Molinari
Brain research May 6, 1996 DOI: 10.1016/0006-8993(96)00056-x via PubMed
Summary
AI-generated from the abstractA novel synthetic compound, 18-methoxycoronaridine (MC), reduces morphine and cocaine self-administration in rats without the tremors and cerebellar toxicity seen with ibogaine. In acute tests, MC decreased drug intake but did not affect bar-press responding for water. In some rats, a single 40 mg/kg dose of MC produced prolonged decreases in morphine or cocaine intake lasting days or weeks. MC showed no tremorigenic effect, and a high dose of 100 mg/kg caused no cerebellar toxicity. Like ibogaine, MC lowered extracellular dopamine levels in the nucleus accumbens. MC appears to be a safer ibogaine-like agent potentially useful for treating addiction.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | 18-Methoxycoronaridine (MC) |
| Dose | 40 mg/kg, 100 mg/kg |
| Citations | 118 |
| Key finding | MC decreased morphine and cocaine self-administration in rats without tremorigenic or cerebellar toxic effects. |
Abstract
Ibogaine, a naturally occurring iboga alkaloid, has been claimed to be effective in treating addiction to opioids and stimulants, and has been reported to inhibit morphine and cocaine self-administration in rats. However, ibogaine also has acute nonspecific side effects (e.g. tremors, decreased motivated behavior in general) as well as neurotoxic effects (Purkinje cell loss) manifested in the vermis of the cerebellum. 18-Methoxycoronaridine (MC) is a novel, synthetic iboga alkaloid congener that mimics ibogaine's effects on drug self-administration without appearing to have ibogaine's other adverse effects. Acutely, in rats, MC decreased morphine and cocaine self-administration but did not affect bar-press responding for water. In some rats, treatment with MC (40 mg/kg) induced prolonged decreases in morphine or cocaine intake lasting several days or weeks. MC had no apparent tremorigenic effect, and there was no evidence of cerebellar toxicity after a high dose (100 mg/kg) of MC. Similar to the effects of ibogaine and other iboga alkaloids that inhibit drug self-administration, MC (40 mg/kg) decreased extracellular levels of dopamine in the nucleus accumbens. MC therefore appears to be a safer, ibogaine-like agent that might be useful in the treatment of addictive disorders.