Pagoclone, GABA, and Stuttering

Pagoclone had previously been tested as a drug to relieve anxiety. One of the participants in the study who stuttered noted that when taking the drug he experienced greater fluency. So it was decided that larger scale trials would be conducted to test the efficacy of pagoclone as an anti-stuttering medication.

Pagoclone is a member of the class of drugs called cyclopyrrolones. However, it acts like a BZ in that it binds to BZ receptor sites on neurons, the difference being that it binds only to some of the subtypes within a BZ binding site, specifically to the alpha-2 and alpha-3 subtypes. Hence, it does not have some of the negative effects of BZs such as causing sleepiness and, it is claimed, less tendency to induce physical dependency, addiction, and tolerance. In any case, pagoclone facilitates the binding of GABA to post-synaptic neurons which in turn inhibits the action of dopamine, implicated in stuttering.

Pagoclone had been in phase 3 drug testing by Endo Pharmaceuticals, but the testing program was abruptly halted recently. No explanation to this date has been given. A number of individuals partaking in the program have anecdotally reported positive results. In most cases disfluency was substantially reduced but not completely eliminated. It would seem that the humane move by Endo would be to test the drug for safety, release it to the public, and let the market determine its fate.

Many individuals who stutter and have not been part of the testing program had been eagerly waiting for pagoclone to reach the market. Many are curious as to whether or not this drug would improve their fluency. Perhaps this question might be answered indirectly by trying a BZ instead. Since the action of the two drugs is basically the same, the extent of fluency improvement using a BZ might give an indication of the potential efficacy of pagoclone for any given individual.