Background: Antipsychotics are divided into typical and atypical compounds based on clinical efficacy and side effects. The purpose of this study was to characterize in vitro a series of novel azecine-type compounds at human dopamine D1-D5and 5HT2Areceptors and to assign them to different classes according to their dopamine/5HT2Areceptor profile. Results: Regardless of using affinity data (pK1values at D1-D5and 5HT2A) or selectivity data (15 log (K1, ratios)), principal component analysis with azecine-type compounds, haloperidol, and clozapine revealed three groups of dopamine/5HT2Aligands: 1) haloperidol; 2) clozapine plus four azecine-type compounds; 3) two hydroxylated dibenzazecines. Reducing the number of K1, ratios used for principal component analysis from 15 to two (the D1/D2and D2/5HT2AK1ratios) obtained the same three groups of compounds. The most potent dibenzazecine clustering in the same group as clozapine was the non-hydroxylated LE410 which shows a slightly different D2-like receptor profile (D2L> D3 > D4.4) than clozapine (D4.4> D2L> D3). The monohydroxylated dibenzacezine LE404 clusters in a separate group from clozapine/LE410 and from haloperidol and shows increased D1, selectivity. Conclusion: In conclusion, two compounds with a novel dopamine/ 5HT2Areceptor profile, LE404 and LE410, with some differences in their respective D1/D2receptor affinities including a validated pharmacophore-based 3D-QSAR model for D1antagonists are presented. © 2006 Hamacher et al; licensee Biomed Central Ltd.
Hamacher, A., Weigt, M., Wiese, M., Hoefgen, B., Lehmann, J., & Kassack, M. U. (2006). Dibenzazecine compounds with a novel dopamine/5HT2Areceptor profile and 3D-QSAR analysis. BMC Pharmacology, 6. https://doi.org/10.1186/1471-2210-6-11