Identification of Psychoplastogenic N,N-Dimethylaminoisotryptamine (isoDMT) Analogues through Structure-Activity Relationship Studies.
Lee E. Dunlap, Arya Azinfar, Calvin Ly, Lindsay P. Cameron, Jayashri Viswanathan, Robert J Tombari, Douglas Myers-Turnbull, Jack C Taylor, Ana Cristina Grodzki, Pamela J Lein, David Kokel, David E. Olson
Journal of Medicinal Chemistry January 24, 2020 DOI: 10.1021/acs.jmedchem.9b01404 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Structure-activity relationship study Peer reviewed |
|---|---|
| Keywords | Neurons Animals Zebrafish Mice N,N-Dimethyltryptamine Hallucinogens Molecular structure Structure-activity relationship Neuronal plasticity |
| Key points | The authors report identifying key features of the psychoplastogenic pharmacophore and using them to develop N,N-dimethylaminoisotryptamine (isoDMT) psychoplastogens that are easier to synthesize, have improved physicochemical properties, and have reduced hallucinogenic potential compared with DMT counterparts. |
Abstract
Ketamine, N,N-dimethyltryptamine (DMT), and other psychoplastogens possess enormous potential as neurotherapeutics due to their ability to potently promote neuronal growth. Here, we report the first-ever structure-activity relationship study with the explicit goal of identifying novel psychoplastogens. We have discovered several key features of the psychoplastogenic pharmacophore and used this information to develop N,N-dimethylaminoisotryptamine (isoDMT) psychoplastogens that are easier to synthesize, have improved physicochemical properties, and possess reduced hallucinogenic potential as compared to their DMT counterparts.
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- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Ketamine use: a review Addiction July 21, 2011
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