Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers.
OBJECTIVE
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.
Samuels
Ebony R
ER
Psychopharmacology Section, University of Nottingham, Division of Psychiatry, Nottingham, UK.
Hou
Ruihua H
RH
Langley
Robert W
RW
Szabadi
Elemer
E
Bradshaw
Christopher M
CM
D000293:Adolescent; D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects*; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000494:pharmacology; D004294:Domperidone / Q000008:administration & dosage* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077487:Pramipexole; D011603:Psychophysiology; D011680:Pupil / Q000187:drug effects; D012025:Reflex, Pupillary / Q000187:drug effects; D016896:Treatment Outcome
D052160:Benzothiazoles; D018492:Dopamine Antagonists; D004294:Domperidone; D000077487:Pramipexole