Neuroendocrine and behavioral effects of the selective kappa agonist spiradoline in Tourette's syndrome: a pilot...

To evaluate the role of opioids in Tourette's syndrome (TS), we performed a dose-response study of the behavioral and neuroendocrine effects of the selective kappa agonist spiradoline mesylate (U-62066E) in five TS patients and five normal control subjects, aged 20 to 47. The intramuscularly administered doses of spiradoline were 0.0, 0.8, 1.6, and 3.2 micrograms/kg. Baseline and postdrug tic frequencies were determined from "blind" videotape tic counts and bedside clinician ratings. In comparison with placebo, the lowest dose of spiradoline was associated with significant decreases in cumulative postdrug counts of total tics and phonic tics, as well as in clinician ratings of postdrug motor tic frequencies. By contrast, there was a trend for tic frequencies to increase following the intermediate dose (1.6 micrograms/kg) of spiradoline. As a group, the TS subjects also secreted significantly more growth hormone following the 1.6 micrograms/kg dose of spiradoline than did the normal control subjects. These preliminary findings provide additional evidence for the involvement of opioids in TS and suggest (1) that opioids may exert dual modulatory effects on the expression of tic symptoms and (2) that some TS patients may be characterized by increased sensitivity of kappa receptors regulating growth hormone secretion.