The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects

Lee Friedman*, John A. Jesberger, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The effects of apomorphine (0.01 mg/kg SC) a direct- acting dopamine (DA) agonist, MK-212 (6-chloro-2-[1- piperazinyJ-pyrazine) (20 mg PO), a direct-acting serotonin (5-HT) agonist, and placebo on smooth pursuit fYe movements were evaluated in 10 to 12 normal volunteers. Smooth pursuit was tested just prior to administration of either apomorphine, MK-212, or placebo (on separate days), and then repeatedly tested at 30 min intervals for two hours after dose administration. Tie smooth pursuit targets were a series of predictable, constant velocity ramps with velocities of 5°/sec (slow target) and 20°/sec (fast target). Eye movements were recorded with infrared oculography, and the following six measures were obtained; steady-state gain (slow-target- gain; fast-target-gain), corrective catch-up saccade (CUS) rate (slow-target-CUS-rate; fast-target-CUS-rate), and CUS amplitude (slow-target-CUS-amplitude; fast-target- CUS-amplitude). The placebo test yielded a statistically significant monotonic decrease over time in slow-target- gain and corresponding increase in slow-target-CUS- rate, but no effects of placebo were noted for the fast target. Apomorphine injection produced a marked reduction in both slow-target-gain and fast-target-gain at 30 min, returning to baseline thereafter. Apomorphine injection also produced a statistically significant increase in slow-target-CUS-amplitude. Ingestion of MK-212 produced a statistically significant increase in slow-target- gain and fast-target-gain as well as a corresponding decrease in slow-target-CUS-rate and fast-target-CUS- rate at 90 min or 120 min. There was evidence that the decline in slow-target-gain after apomorphine was associated with side-effects such as sleepiness, but the decline in fast-target-gain was not related to side-effects. The improved smooth pursuit performance after MK-212 was not related to side-effects. The data suggest that serotoninergic stimulation can improve smooth pursuit performance, whereas dopaminergic stimulation worsens this performance.

Original languageEnglish (US)
Pages (from-to)49-62
Number of pages14
JournalNeuropsychopharmacology
Volume11
Issue number1
DOIs
StatePublished - Aug 1994

Keywords

  • Apomorphine
  • Dopamine
  • Gain
  • MK-212
  • Normal volunteers
  • Serotonin
  • Smooth pursuit

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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