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Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers

Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers
Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers
AIMS: To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. METHODS: Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. RESULTS: The pre-post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole -15.75 (-23.38, -8.13), combination -11.84 (-20.77, -2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F(3,45) = 8.39, P < 0.001), initial diameter of the light reflex response (F(3,42) = 3.78, P < 0.05), and light (F(3,45) = 5.21, P < 0.005) and dark (F(3,45) = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations. CONCLUSIONS: The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone had access to some central D2-receptors
psychiatry, autonomic nervous system, administration & dosage, adult, adolescent, treatment, darkness, dopamine, pupil, drug effects, blood, flicker fusion, pharmacology, salivation, dopamine antagonists, methods, benzothiazoles, endocrine system, male, comparison, blood pressure, treatment outcome, domperidone, humans, prolactin, heart rate, pupillary, dose-response relationship, reflex, drug, psychophysiology
0007-1188
591-602
Samuels, E.R.
be1fd344-e73a-43da-aca8-33c6e21cb7f2
Hou, R.H.
470bdcbc-93a9-4dad-aac5-26d455c34376
Langley, R.W.
579cc42e-972f-4422-952f-1c76ecc4b4e3
Szabadi, E.
cff688f8-264f-4ca3-a2c4-cb10930f1956
Bradshaw, C.M.
0baafd10-0e91-4113-b90b-27132bd77305
Samuels, E.R.
be1fd344-e73a-43da-aca8-33c6e21cb7f2
Hou, R.H.
470bdcbc-93a9-4dad-aac5-26d455c34376
Langley, R.W.
579cc42e-972f-4422-952f-1c76ecc4b4e3
Szabadi, E.
cff688f8-264f-4ca3-a2c4-cb10930f1956
Bradshaw, C.M.
0baafd10-0e91-4113-b90b-27132bd77305

Samuels, E.R., Hou, R.H., Langley, R.W., Szabadi, E. and Bradshaw, C.M. (2007) Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers. British Journal of Pharmacology, 64 (5), 591-602.

Record type: Article

Abstract

AIMS: To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. METHODS: Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. RESULTS: The pre-post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole -15.75 (-23.38, -8.13), combination -11.84 (-20.77, -2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F(3,45) = 8.39, P < 0.001), initial diameter of the light reflex response (F(3,42) = 3.78, P < 0.05), and light (F(3,45) = 5.21, P < 0.005) and dark (F(3,45) = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations. CONCLUSIONS: The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone had access to some central D2-receptors

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More information

Published date: 2007
Keywords: psychiatry, autonomic nervous system, administration & dosage, adult, adolescent, treatment, darkness, dopamine, pupil, drug effects, blood, flicker fusion, pharmacology, salivation, dopamine antagonists, methods, benzothiazoles, endocrine system, male, comparison, blood pressure, treatment outcome, domperidone, humans, prolactin, heart rate, pupillary, dose-response relationship, reflex, drug, psychophysiology

Identifiers

Local EPrints ID: 62566
URI: http://eprints.soton.ac.uk/id/eprint/62566
ISSN: 0007-1188
PURE UUID: 3a63a1bc-8308-4545-b606-12dbf8460fd0
ORCID for R.H. Hou: ORCID iD orcid.org/0000-0001-6127-1478

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Date deposited: 09 Sep 2008
Last modified: 09 Jan 2022 03:25

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Contributors

Author: E.R. Samuels
Author: R.H. Hou ORCID iD
Author: R.W. Langley
Author: E. Szabadi
Author: C.M. Bradshaw

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