A molecular theory of recognition and activation at a 5-HT receptor based on a quantum chemical approach to structure activity relationships.

The study of structure activity relationships (SAR) is based on the delineation of the causal relationships between the properties of molecules and the observed responses evoked by the interaction of these molecules with biological systems. The methods of theoretical and quantum chemistry describe accurately the molecular properties that are determined by molecular structure and provide a rigorous link between structure and activity. We study the molecular events in the pharmacological mechanism of drugs interacting with the receptor of 5-hydroxytryptamine (5-HT, serotonin) by defining the elements of recognition and by analyzing the changes induced in a molecular model for the receptor. These steps define the relationship between the properties of the drugs and their ability to be recognized and cause the activation of the receptors. Consequently, our quantum chemical studies of drug-receptor interactions explain the selectivity of receptors and the molecular determinants for agonism and antagonism on the 5-HT receptor.