Molecular properties of psychopharmacological drugs determining non-competitive inhibition of 5-HT3A receptors

We developed a structure–property–activity relationship (SPAR)-model for psychopharmacological drugs acting as non-competitive 5-HT3A receptor antagonists by using a decision-tree learner provided by the RapidMiner machine learning tool. A single molecular descriptor, namely the molecular dipole moment per molecular weight (μ/MW), predicts whether or not a substance non-competitively antagonizes 5-HT-induced Na+ currents. A low μ/MW is compatible with drug-cumulation in apolar lipid rafts. This study confirms that size-intensive descriptors allow the development of compact SPAR models.

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