Our laboratories interest can be broadly defined as the examination of the biological mechanisms of therapeutic agents (e.g., anticancer, antibiotics, neurological) at the molecular level; the synthesis of peptidomimetics; and the discovery, development and evaluation of new medicinal agents.
In recent years, we have focused on neurological disorders. Epilepsy and neuropathic pain are major neurological disorders that affect all populations. Epilepsy refers to the many types of recurrent seizures produced by paroxysmal excessive neuronal discharges in the brain. The mainstay of treatment has been the long-term and consistent administration of anticonvulsant drugs. Unfortunately, current medications are ineffective for approximately one-third of patients with epilepsy. Moreover, none of the clinical agents are capable of achieving total seizure control and most have disturbing side-effects. Neuropathic pain is chronic pain that is due to dysfunction or disease of the nervous system at the peripheral level, the central level, or both. It includes pain syndromes from cancer, diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, and others. Recent pharmacological studies in our laboratory have led to the discovery of a new series of highly stereoselective anticonvulsant agents. The lead compound, lacosamide ((R)-N-benzyl-2-acetamido-3-methoxypropionamide), has emerged from phase III clinical trials for the treatment of epilepsy and neuropathic pain and has been submitted for regulatory approval. One major objective in our laboratory is to identify and characterize the sites and mechanisms of lacosamide function and to advance molecular tools useful to elucidate the pathways leading to seizure and neuropathic pain control. Powerful techniques at the interface of chemistry and biology are integrated to address this specific aim. A second laboratory objective is to develop a new series of medicinal agents for these and other neurological disorders. |