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Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine functions in healthy volunteers

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Abstract

Rationale

In a previous study in healthy volunteers, the anti-Parkinsonian drug pramipexole caused sedation and pupil dilatation, consistent with the stimulation of inhibitory D2/D3 autoreceptors on the ventral tegmental area dopaminergic neurones. The sedation may be related to the removal of the dopaminergic excitation of the locus coeruleus (via the meso-coerulear pathway), whereas the pupil dilatation may be due to the removal of the dopaminergic excitation of the Edinger–Westphal nucleus (via a putative meso-pupillomotor pathway).

Objectives

We investigated the hypothesis that amisulpride, a D2/D3 receptor antagonist, would have effects opposite to those of pramipexole on alertness, pupillary and endocrine functions.

Materials and methods

Pramipexole (0.5 mg), amisulpride (50 mg), and their combination were administered to 16 healthy males in a balanced, cross-over, double-blind design. Tests included measures of alertness (Pupillographic Sleepiness Test, critical flicker fusion frequency, visual analogue scales), pupillary functions (resting pupil diameter, light and darkness reflex responses), non-pupillary autonomic functions (heart rate, blood pressure, salivation, core temperature), and endocrine functions [blood concentrations of prolactin, growth hormone (GH) and thyroid stimulating hormone (TSH)]. Data were analysed by ANOVA.

Results

Pramipexole reduced alertness and pupillary light reflex response amplitude, tended to reduce core temperature, reduced prolactin levels and increased GH levels. Amisulpride reduced pupil diameter, increased the amplitude of the light reflex response and prolactin and TSH levels.

Conclusions

The opposite effects of pramipexole and amisulpride on alertness, pupillary function and pituitary hormone levels are consistent with their interactions with inhibitory D2/D3 receptors on VTA neurones and in the tuberoinfundibular system.

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Acknowledgement

ERS is an Institute of Neuroscience, University of Nottingham, Scholar.

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Authors and Affiliations

  1. Psychopharmacology Section, Division of Psychiatry, University of Nottingham Medical School (Room B109), Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    E. R. Samuels, R. H. Hou, R. W. Langley, E. Szabadi & C. M. Bradshaw

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  1. E. R. Samuels
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  2. R. H. Hou
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  3. R. W. Langley
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  4. E. Szabadi
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Correspondence to E. Szabadi.

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Samuels, E.R., Hou, R.H., Langley, R.W. et al. Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine functions in healthy volunteers. Psychopharmacology 187, 498–510 (2006). https://doi.org/10.1007/s00213-006-0443-y

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