Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids.
Alexander J Hughes, Charles R Hamelink, Steven D Townsend
European journal of organic chemistry September 23, 2024 DOI: 10.1002/ejoc.202400432 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Ibogaine |
| Keywords | Iboga alkaloids Ibogamine Total synthesis |
| Citations | 5 |
| Key findings | Ibogaine reduces self-administration of several addictive substances in rodents but has cardiotoxicity and hallucinogenic effects that limit its use in humans, prompting drug discovery efforts. |
Abstract
The iboga alkaloids are a family of monoterpene indole alkaloids first discovered from the root of Tabernanthe iboga. The major alkaloid constituent in the root, ibogaine, has garnered interest for its anti-addictive properties. Ibogaine has been shown to reduce opiate, amphetamine, alcohol, and nicotine self-administration in rodents. However, ibogaine itself is less than optimal as a treatment in humans for Substance Abuse Disorder (SUD) due to its cardiotoxicity and hallucinogenic potential. Instead, ibogaine is an attractive lead for drug discovery efforts. Indeed, several notable programs have been launched to both elucidate ibogaine's mechanism of action and reduce its toxicity. While there have been over twenty total syntheses of ibogamine, ibogaine, and closely related family members, there are far fewer syntheses of recently isolated iboga alkaloids. In this targeted review, we discuss the synthetic strategies applied to the synthesis of classical and non-classical iboga alkaloids.