@article {L. Berger:2012:0929-8673:3044,
title = "Screening of 64 Tryptamines at NMDA, 5-HT1A, and 5-HT2A Receptors: A Comparative Binding and Modeling Study",
journal = "Current Medicinal Chemistry",
parent_itemid = "infobike://ben/cmc",
publishercode ="ben",
year = "2012",
volume = "19",
number = "18",
publication date ="2012-06-01T00:00:00",
pages = "3044-3057",
itemtype = "ARTICLE",
issn = "0929-8673",
url = "https://www.ingentaconnect.com/content/ben/cmc/2012/00000019/00000018/art00011",
doi = "doi:10.2174/092986712800672058",
keyword = "endogenous, alkyl or halogen, NMDA receptor, ketanserin binding, Free-Wilson Analysis, MOE descriptors, QSARs, T derivatives (Ts), 5-HT receptor, Substituted tryptamines",
author = "L. Berger, M. and Palangsuntikul, R. and Rebernik, P. and Wolschann, P. and Berner, H.",
abstract = "Tryptamine (T) and several T derivatives (Ts) inhibit in a voltage-dependent manner the NMDA receptor (NR). This effect is influenced by substituents at various positions, but has not yet been subjected to a detailed SAR study. Here, 64 Ts have been tested as inhibitors of [3H]MK-801
binding to NRs on rat brain membranes. For comparison, they were also tested as inhibitors of [3H]8-OHDPAT binding to 5-HT1A and of [3H]ketanserin binding to 5-HT2A receptors. Since most of these Ts have not been tested before at any of these receptors, we start with a review of the effects
of Ts on 5-HT1A and 5-HT2A binding sites. NRs were inhibited with IC50s from 2 to 7 M by Ts with alkyl or halogen at positions 2, 5, and/or 7. Inhibition by some Ts was attenuated more than 10-fold by 30 M spermine. The most potent inhibitors at 5-HT1A receptors were 5-carboxamido-T
(IC50 0.00015 M) and serotonin (0.0016 M), at 5-HT2A receptors 2-Me-4,7-Cl2-T (1.2 M) and 2,7-Me2-4-Cl-T (2.0 M). Fujita-Ban modified Free-Wilson analyses pointed to the individual significance of particular substituents. Also QSARs based on molecular operating environment
descriptors resulted in sound correlations at all 4 targets. No similarities between the NR and 5-HT receptors could be found. At the NR, only L-Trp-NH2 bound 10 times better than at both 5-HT receptors studied. L-Trp-NH2 may be a structural lead to endogenous non-competitive NR antagonists.",
}