Application of classical and contemporary (e.g. receptor graphics modeling) medicinal chemistry drug design techniques to develop 1) therapeutic agents for the potential treatment of central and neurological disorders (e.g. anxiety, depression, schizophrenia, Alzheimer’s disease), and 2) pharmacological tools (e.g. radioligands, selective agonists and antagonists, or autoradiographic and radioimaging agents) to interrogate drug-receptor interactions at G-protein coupled and ion channel receptors. More specifically, we utilize drug design, chemical synthesis, and preclinical evaluations using various functional assays (i.e., in vitro and in vivo techniques, such as radioligand binding and behavioral drug discrimination) to develop receptor selective- and receptor subtype-selective agents as agonists and/or antagonists (or partial agonists, inverse agonists) at selected receptor populations [e.g. serotonin 5-HT1 – 5-HT7 receptors, nicotinic (e.g. alpha4beta2 and other) cholinergic receptors, sigma receptors, imidazoline receptors]. Specific interests include modulation of DARPP by serotonergic ligands, classification and mechanism of action studies of drugs of abuse (e.g. classical hallucinogens, central stimulants, and certain designer drugs), and agonist-directed receptor trafficking. Other interests involve allosteric modulation of receptors by synthesis and evaluation of novel agents that act at receptor sites not utilized by standard orthosteric neuromodulators/neurotransmitters, receptor dimerization (homo- and hereto-dimerization), and application of classical SAR and QSAR techniques to determine what/how various structural features of drugs influence their receptor binding properties and pharmacological action.
