Landon M Klein

Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

2 papers in the library · 124 citations · publishing 2015-2018

Papers

N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues.

ACS chemical neuroscience July 15, 2015 David E Nichols, M Flori Sassano, Adam L Halberstadt et al. 81 citations

A series of N-benzylated-5-methoxytryptamine analogues and a parallel series of N-benzylated 2C-I analogues were synthesized and tested. Most compounds showed highest affinity for 5-HT2 family receptors. Para substitution on the benzyl group reduced affinity, while ortho or meta substitution enhanced it. Large lipophilic groups improved affinity but often reduced functional activity. Functional testing at human and rat 5-HT2A, 5-HT2B, and 5-HT2C receptors revealed no general correlation between affinity and function. Several tryptamine congeners were potent functional agonists (EC50 values from 7.6 to 63 nM) but mostly partial agonists. In the mouse head twitch assay, many compounds induced head twitches, and this behavior correlated significantly with functional potency at the rat 5-HT2A receptor.

DOI: 10.1021/cn500292d Full text Serotonin 5-ht2 receptors 5-ht2a 5-methoxytryptamine +4

Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs.

Neuropharmacology November 1, 2018 Landon M Klein, Nicholas V Cozzi, Paul F Daley et al. 43 citations

Most DALT derivatives bind to several serotonin receptors, sigma sites, and other targets. In mice, several compounds triggered the head-twitch response, a behavioral proxy for hallucinogen effects, with 4-acetoxy-DALT being most potent, followed by 5-fluoro-DALT, 5-methoxy-DALT, 4-hydroxy-DALT, DALT, and 5-bromo-DALT; four derivatives did not induce the response. Head-twitch potency was not linked to binding affinity at either 5-HT1A or 5-HT2A receptors alone, but a regression analysis showed that 5-HT2A receptors contribute positively and 5-HT1A receptors contribute negatively to potency, explaining 87% of the variance. These results support the role of 5-HT2A receptors in the head-twitch response and suggest that 5-HT1A activation by tryptamine hallucinogens dampens this effect.

DOI: 10.1016/j.neuropharm.2018.02.028 Full text 4-aco-dalt 4-Acetoxy-N,N-Diallyltryptamine 4-Hydroxy-N,N-Diallyltryptamine 5-MEO-Dalt +8