Mallinckrodt Pharmacology Research Unit
The mission of the Mallinckrodt Pharmacology Research Unit is to elucidate the molecular mechanisms by which general anesthetics act. Although some 25 million general anesthetics are given each year in the U.S. alone, the underlying mechanisms by which general anesthetics act are still poorly understood, but these agents are used at high concentrations and exhibit many unwanted side effects. The overall working hypothesis adopted by the Unit's researchers is that the depression in neuronal excitability leading to general anesthesia results from the capacity of anesthetics to enhance the actions of inhibitory channels and to inhibit the action of excitatory channels. The major focus is on the Cys-loop ligand-gated ion channel superfamily that contains the inhibitory channels gated by GABA and glycine and the excitatory channels gated by acetylcholine and serotonin. Other channels whose role in anesthesia is under study include the excitatory channels gated by glutamate and the inhibitory tandem pore potassium channels.