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

Psychopharmacology Section, University of Nottingham, Division of Psychiatry, Nottingham, UK.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 12/2007; 64(5):591-602. DOI: 10.1111/j.1365-2125.2007.02938.x
Source: PubMed


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.
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.
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.
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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    • "In the current study, we report tentative findings suggesting that pramipexole reduced the learning rate rather than affecting the reward sensitivity, which might correspond to a direct reduction in the signal reported by phasic DA. Although pramipexole is a non-ergot D 2/D3agonist (and is clinically used as such in Parkinson’s disease, restless leg syndrome, and occasionally in treatment-resistant MDD), it has previously been found to have behavioural effects of a DA antagonist at the low doses (0.5 mg) used in our dataset [72-74]. Similarly, low doses of the D 2 agonist cabergoline have been found to specifically reduce reward go learning [75]. "
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    • "In terms of limitations, it should be noted that the peripheral D 2 antagonist domperidone was administered on both testing days. Whilst domperidone is generally assumed not to cross the blood–brain barrier, there is some evidence that the effects of domperidone and pramipexole differ from pramipexole alone (Samuels et al., 2007). However, domperidone is useful for preventing nausea and sickness clinically (Parkes, 1986) and proved effective for these purposes in this study. "
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