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

doi:10.1038/npp.1994.35

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

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

12 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 language	English (US)
Pages (from-to)	49-62
Number of pages	14
Journal	Neuropsychopharmacology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/npp.1994.35
State	Published - Aug 1994

Funding

This research was supported by USPHS grants MH-47574 (to Dr. Friedman), MH-41684 (to Dr. Meltzer) and GCRC M01RR00080, by the Department of Veterans Affairs and grants to Dr. Meltzer from the Elisabeth Severance Prentiss, John Pascal Sawyer and Laureate Foundations. HYM is the recipient of a USPHS Research Career Scientist Award (MH 47808).

Keywords

Apomorphine
Dopamine
Gain
MK-212
Normal volunteers
Serotonin
Smooth pursuit

ASJC Scopus subject areas

Psychiatry and Mental health
Pharmacology

Access to Document

10.1038/npp.1994.35

Cite this

@article{3727a15e73834e779b6a49676933ec6a,

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

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.",

keywords = "Apomorphine, Dopamine, Gain, MK-212, Normal volunteers, Serotonin, Smooth pursuit",

author = "Lee Friedman and Jesberger, \{John A.\} and Meltzer, \{Herbert Y.\}",

note = "Funding Information: This research was supported by USPHS grants MH-47574 (to Dr. Friedman), MH-41684 (to Dr. Meltzer) and GCRC M01RR00080, by the Department of Veterans Affairs and grants to Dr. Meltzer from the Elisabeth Severance Prentiss, John Pascal Sawyer and Laureate Foundations. HYM is the recipient of a USPHS Research Career Scientist Award (MH 47808).",

year = "1994",

month = aug,

doi = "10.1038/npp.1994.35",

language = "English (US)",

volume = "11",

pages = "49--62",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects

AU - Friedman, Lee

AU - Jesberger, John A.

AU - Meltzer, Herbert Y.

N1 - Funding Information: This research was supported by USPHS grants MH-47574 (to Dr. Friedman), MH-41684 (to Dr. Meltzer) and GCRC M01RR00080, by the Department of Veterans Affairs and grants to Dr. Meltzer from the Elisabeth Severance Prentiss, John Pascal Sawyer and Laureate Foundations. HYM is the recipient of a USPHS Research Career Scientist Award (MH 47808).

PY - 1994/8

Y1 - 1994/8

N2 - 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.

AB - 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.

KW - Apomorphine

KW - Dopamine

KW - Gain

KW - MK-212

KW - Normal volunteers

KW - Serotonin

KW - Smooth pursuit

UR - http://www.scopus.com/inward/record.url?scp=0028023779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028023779&partnerID=8YFLogxK

U2 - 10.1038/npp.1994.35

DO - 10.1038/npp.1994.35

M3 - Article

C2 - 7945744

AN - SCOPUS:0028023779

SN - 0893-133X

VL - 11

SP - 49

EP - 62

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 1

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this