Investigating Drug Interactions: From Thermodynamic Driving Forces Of Ligand Binding To In Vivo Multiphoton Microscopy Of Chemotherapy Drug Intrinsic Fluorescence

In 1905, Langley introduced the concept of a -receptive substance[DOUBLE VERTICAL LINE]. He theorized these substances were different in different species and together with the findings of Paul Ehrlich and A.J. Clark the field of receptor theory was born. Since then, biological, biophysical and biochemical methods of investigation have led us to identify not only -substances[DOUBLE VERTICAL LINE] but also their molecular targets, how they're involved in physiological mechanisms, and the roles they play when a disease state develops. Pharmacological interactions can be dissected into basic thermodynamic forces that contribute to drug binding to receptor targets. Here we investigate the driving forces of ligand-binding to a soluble protein, GluAs1s2 using displacement isothermal titration calorimetry. Langley was correct in his theory about the diversity of substances, and we exploit this diversity by investigating the effects of cocaine and cocaine metabolites on several neuronal nACh receptor subtypes using two-electrode voltage clamp and the Xenopus laevis oocyte expression system. Lastly, we utilize the intrinsic fluorescence of a chemotherapy drug to investigate its potential as a diagnostic tool in vivo