Current Research Projects

Exploring of Multi-Target Psychostimulant Reward. While many advances have been made toward understanding psychostimulant addiction, currently there is a lack of information on how the specific interactions of METH and MDMA with the monoamine systems [dopamine (DA), serotonin (5-HT) and norepinephrine (NE)] leads to the overall psychostimulant effect and abuse liability of these amphetamine-based drugs. The lack of this fundamental knowledge is believed to contribute to the current failure to develop a therapeutic agent or strategy for the treatment of METH and MDMA abuse and/or the associated withdrawal and craving.

The focus of our research is designed to provide a greater understanding of how the three monoaminergic systems contribute to the psychostimulant effects of METH and MDMA and how different levels of activation of monoamine transporters contribute to the efficacy of these two drugs. The goal of these studies is to use molecules with unique molecular scaffolds and novel ratios of monoaminergic transporter affinities as molecular probes to systematically establish a spectrum of neurotransmitter activation as it relates to the stimulant and rewarding effects METH and MDMA. To this end, we are focused on studying the interactions between the dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET) in mediating the behavioral effects of METH and MDMA, highlighting the differences in specific transporter activation. To do this, we have designed novel monoamine transporter ligands (tropanes and azetidines) that display a breadth of affinities and selectivities for the monoamine transporters that serve as molecular probes for transporter activation by METH and MDMA. The ability of these molecular probes to block the locomotor stimulant and rewarding effects of METH and MDMA then can be related to the relative level of activation of each monoamine transporter by METH and MDMA. By changing substituents on these molecular scaffolds we have been able to tune the selecitivity of the compound. This in turn will provide a relative profile of transporter activation for METH and MDMA for comparison, which will provide a basis for the future development of treatments for the abuse of these amphetamine-like drugs.

DAT/SERT/NET Tunable Pharmacophores

Trudell1

 

 

 

 

 

 

 

Iridium Catalyzed C-N Bond Formation.The development of new synthetic methods and the construction of novel nitrogen heterocyclic compounds is a general focus of the research efforts in my group. We have recently developed new methods for carbon-nitrogen bond formation based on the alkylation of amines with alcohols catalyzed by iridium complexes. In addition, we have extended this methodology for the alkylation of amides, sulfonamides and imides. These methods that we have developed for simple substrates are currently under investigation for the synthesis of more complex natural products and pharmacologically interesting compounds.

Ir Catalyzed Alkylation of Amines, Amides and Sulfonamides with Alcohols

Trudell 2

 

 

 

 

Ir Catalyzed N-Heterocyclization of Amines for Natural Product Synthesis

Trudell 3

.