Dextromethorphan (DM) is a well-known drug commonly used in over-the-counter cough syrups. In most people, DM is rapidly degraded by enzymes in the liver, so very little of it ever gets into the brain. When DM is combined with the drug quinidine, however, the drug is able to cross the blood brain barrier and exert some rather profound neurologic effects. This happens because quinidine blocks a liver enzyme (Cytochrome 2D6) that usually degrades the DM.
During studies on patients suffering from amyotrophic lateral sclerosis (ALS), favorable results occurred among subjects receiving the DM/quinidine combination. These benefits included dramatic reductions in a condition which is commonly referred to as “emotional lability” or “pseudobulbar affect,” a diagnostic term which is difficult to wrap one’s brain around but is medically correct.
Research at CNS, later improved upon by Avanir Pharmaceutical Corporation, led to FDA approval of Nuedexta in 2010 for the treatment of emotional lability that occurs in a variety of neurological conditions, including ALS and multiple sclerosis.
More recently, Nuedexta was shown to enhance speech and swallowing in ALS patients in a controlled study, the first time these critical functions have been improved upon in this disorder.
Circling back to the work that prompted us to undertake studies with DM as a potential treatment for ALS, the Center has initiated a number of collaborations. One of these is exploring in detail the effects of DM on the brain. The other is focused on developing second and third generation pharmaceuticals which may be even more effective in treating neurological conditions.