Emotional lability is a discomforting syndrome observed in ALS patients. Presently, there is no satisfactory treatment for this condition. Dextromethorphan (DM) combined with non- therapeutic doses of quinidine (Q) may control this condition and improve quality of life. Efficacy of the DWQ product is based on producing therapeutic blood levels of DM by using Q to inhibit the extremely rapid metabolism of DM. This research proposal is designed to determine in humans: the minimum dose of Q required to convert extensive metabolizes of DM to poor metabolizes; the pharmacokinetic parameters of DWQ in single and multiple doses; and to develop a stable oral formulation of DAVQ. Two clinical trials in healthy volunteers are proposed. The first, to determine the lowest effective Q dose, will evaluate metabolism of a fixed DM dose as a function of Q doses ranging from 20-150 mg. daily. The second trial """""""" determine DM pharmacokinetics following single and multiple dosing of the DWQ ratio that converted 100 percent of the EM to PM. Preformulation, formulation development and stability studies would be carried out on the appropriate DM/Q product ratio to develop a dosage form for future clinical trials in ALS patients.
