Clinical activity of GABA agonists in neuroleptic- and L-dopa-induced dyskinesia.
It is well known that the therapeutic effect of neuroleptics is counterbalanced by the property of these drugs to induce serious neurological side-effects mainly represented by tardive dyskinesia. Several reports indicate that at the experimental level GABA agonists interact with dopamine neurons with effects on behavior, stereotyped and dyskinetic movements induced by either lesions or dopamine agonists. This action on dopamine-related events provides a basis for a possible therapeutic action of GABA agonists in dyskinesia. Previous results with the GABA agonists muscimol and THIP in tardive dyskinesia have not been encouraging. The present paper deals with clinical results obtained with the new GABA agonist progabide both in neuroleptic-induced dyskinesia and in L-dopa-induced dyskinesia from five studies conducted on a total of 57 patients. Twenty-nine patients suffering from neuroleptic-induced dyskinesia have been treated in three studies (two open, one double-blind cross over) with progabide at doses from 900 to 2400 mg/day; clinical evaluation and EMG testing are in favor of a therapeutic effect of progabide on dyskinesia. Twenty-eight patients with L-dopa dyskinesia have been studied in two double blind trials. At variance with studies in tardive dyskinesia progabide was not effective in this kind of dyskinesia but an increase in the "on" time has been observed in both studies. Attempts to treat tardive dyskinesia with various pharmacological tools are reviewed and discussed, showing that at present no established effective treatment exists for this frequent complication of neuroleptic use. The possible mechanism of action of progabide in dyskinesia is discussed in the light of its pharmacological properties. These results suggest that progabide can be useful in the treatment of neuroleptic-induced dyskinesia.
Morselli
P L
PL
Fournier
V
V
Bossi
L
L
Musch
B
B
D014150:Antipsychotic Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D004576:Electromyography; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use
D014150:Antipsychotic Agents; C017985:progabide; D007980:Levodopa; D005680:gamma-Aminobutyric Acid