Nature
January 1, 2021
Lindsay P Cameron, Robert J Tombari, Ju Lu et al.
468 citations
Ibogaine, a psychedelic alkaloid, shows anti-addictive effects in humans and animals but has safety issues including toxicity and heart arrhythmias. Researchers engineered tabernanthalog, a water-soluble, non-hallucinogenic, non-toxic analogue made in a single step. In rodents, tabernanthalog promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects. This demonstrates that careful chemical design can create safer, non-hallucinogenic variants of psychedelic compounds with therapeutic potential.
Nature chemistry
March 1, 2025
Rishab N Iyer, David Favela, Andras Domokos et al.
22 citations
A new chemical method produces ibogaine in seven steps from pyridine, enabling gram-scale synthesis. This approach also creates three additional iboga alkaloids, the unnatural enantiomer (+)-ibogaine, and four analogues. Biological tests show that (+)-ibogaine does not affect cortical neuron growth like natural ibogaine, while (-)-10-fluoroibogamine strongly promotes neuron growth and potently modulates the serotonin transporter. The work provides a platform for making iboga alkaloids and related compounds for further study, supporting research into their therapeutic potential for addiction and other neuropsychiatric conditions.
Cell biology and toxicology
January 29, 2025
Xiaoming Ji, Zhimin Huang, Chenming Zhou et al.
6 citations
Esketamine, a new antidepressant, reduces depressive-like behavior in mice with neuropathic pain by boosting levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, which binds to GluA1 mRNA and promotes m6A modification, enhancing GluA1 expression at synapses. This mechanism offers new insights into esketamine's potential applications and therapeutic avenues for neuropathic pain and depressive behavior.
Natural product reports
March 4, 2021
Rishab N Iyer, David Favela, Guoliang Zhang et al.
Iboga alkaloids, a family of natural products including the anti-addictive compound ibogaine and the chemotherapeutic precursor catharanthine, have inspired chemists and biologists for over 120 years. This review covers advances from 2000 to 2020 in their biosynthesis and chemical synthesis, as well as their development as next-generation neurotherapeutics for mental illness. The authors provide historical context for recent discoveries and highlight unresolved questions. Although significant progress in chemistry and pharmacology has occurred since the 1960s, the iboga alkaloids continue to drive scientific innovation.