Nmda Antagonists Are Useful in Pd: No

The search for antiglutamatergic drugs useful in PD is burdened by great expectations and disappointing results. At least 35 years of literature production can be tracked, and overwhelming theoretical evidence suggests that antiglutamatergic drugs could or should be useful in PD, yet evidence of positive results is restricted to few decent, blinded studies and to a massive presentation of anecdotal reports, never reaching the sufficient impact to generate a reliable meta-analysis. Among tested drugs, one may quote MK-801, Amantadine, Memantine, Sarizotan, Destrometorphan, Acamprosate, none of which is endowed with the outstanding evidence that it is (not may be but " is ") useful in PD. MK-801 has undoubtedly the widest background support of experimental pharmacological evidence of its antiglutamatergic activity, yet its toxicity forbade clinical application. Sarizotan was prescribed as a drug useful to reduce dyskinesias in PD, (as dyskinesias should be reduced by anti-NMDA drugs). Yet the clinical trial ended in a disappointing failure. Dextrometorphan was tested in PD only in anecdotal reports. It found its role in international pharmacopeia as a cough syrup and only recently, produced in a formulation associated with low dose quinidine sulfate in order to enable its concentration in central nervous system, found a new role for the treatment of pseudobulbar affect. No trials were produced in PD patients. Acamprosate was recently introduced for the treatment of alcoholism, and supposedly should reduce impulse control disorder (ICD) in PD and, again, supposedly also dyskinesias: yet no studies are supporting these suppositions. Mementine has been on the shelf as anti-NMDA drug for 30 years: recently it found a role for the treatment of dementia. Its usefulness in PD or PD with Dementia is, modestly, supported in studies performed in small numbers of patients. As any other drug used for the treatment of cognitive disorders, Memantine is burdened by a lower than 1/7 ratio for Numbers Needed to Treat (NNT): the objection that several other useful drugs are characterized by lower NNTs cannot be accepted in PD, as in this disease the operating physicians are spoiled by direct (not just statistical) evidence of how and when a drug works. Beyond these putative effects on cognitive disorders, few anecdotal reports evidenced that Memantine might reduce dyskinesias, yet no sufficient evidence was deemed to exist as a support to this hypothesis. Amantadine is a case apart: born as an anti-flu agent, the discovery of its efficacy in PD was …