Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors

Mierau, Joachim; Schneider, Franz J.; Ensinger, Helmut A.; Chio, Christopher L.; Lajiness, Mary E.; Huff, Rita M.

doi:10.1016/0922-4106(95)90013-6

Cited by 233 publications

(153 citation statements)

References 18 publications

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“…In intact dopaminergic systems and at lower doses, pramipexole primarily stimulates presynaptic autoreceptors of the D3 and D2 type, thereby reducing the synthesis and synaptic release of DA. Stimulation of D2 and D3 postsynaptic receptors is observed with reduced DA release due to loss or damage of the presynaptic terminations (Mierau et al, 1995). Specifically, in patients with PD, pramipexole imparts its therapeutic effects on motor deficits through the postsynaptic D2 and D3 receptors to correct an imbalance between the direct and the indirect striatofugal nerve tracts by enhancing the direct transmission (through D3 receptors) and reducing the indirect transmission (through D2 receptors; (Mierau et al, 1995)).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike psychostimulant medications, it has an eightfold greater affinity for D3 over the D2 receptor (Mierau et al, 1995;Gerlach et al, 2003) and it acts on presynaptic and on postsynaptic receptors (Piercey, 1998). In intact dopaminergic systems and at lower doses, pramipexole primarily stimulates presynaptic autoreceptors of the D3 and D2 type, thereby reducing the synthesis and synaptic release of DA.…”

Section: Discussionmentioning

confidence: 99%

“…Low doses of pramipexole (eg, 0.25-0.5 mg) are thought to influence reward via a paradoxical effect related to activation of the presynaptic D2 autoreceptor, resulting in a blockade of phasic DA release and a blunted response to rewarding stimuli (Riba et al, 2008). In contrast, higher doses of pramipexole, including those in the range used to treat PD, act as specific agonists both presynaptically and postsynaptically to enhance dopaminergic activity (Mierau et al, 1995), which may be more relevant to the potential to induce compulsive behaviors, such as pathological gambling, although the specific distinctions have not been directly demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

Burdick

Braga

Gopin

et al. 2013

Neuropsychopharmacol

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We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre-and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F ¼ 0.63; p ¼ 0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group's pattern was similar to that reported in healthy individuals (treatment Â time Â block interaction, po0.05). Analyses of choice strategy using the expectancy valence model revealed that after 8 weeks on pramipexole, BPD patients attended more readily to feedback related to gains than to losses, which could explain the impaired learning. There were no significant changes in mood symptoms over the 8 weeks, and no increased propensity toward manic-like behaviors were reported. Our results suggest that the enhancement of dopaminergic activity influences risk-associated decision-making performance in euthymic BPD. The clinical implications remain unknown.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

Burdick

Braga

Gopin

et al. 2013

Neuropsychopharmacol

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“…It displays submicromolar affinity for D 2 and D 3 receptors, but micromolar affinity also for D 1 , D 4 , and D 5 . It also showed some affinity (at submicromolar to micromolar concentrations) for the 5-HT 3 and 5-HT 4 serotonin receptors (20,21). As the normal adrenal cortex, and even more so the APA, can express 5HT 4 , which on binding serotonin released from mast cells can elicit aldosterone secretion (22), it might be argued that some of the metoclopramide effects seen in this study occurred via serotonin receptors.…”

Section: Discussionmentioning

confidence: 94%

Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

Seccia¹,

Miotto²,

Toni³

et al. 2011

European Journal of Endocrinology

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Background: Adrenal vein sampling (AVS) is the gold standard for identifying the surgically curable forms of primary aldosteronism. Dopamine modulates adrenocortical steroidogenesis and tonically inhibits aldosterone secretion via D 2 receptor. However, whether it could also affect the release of cortisol and chromogranin A (ChA), which can be used to assess the selectivity of AVS, is unknown. Objective: To investigate whether metoclopramide increased the release of cortisol and ChA and could thereby improve assessment of the selectivity at AVS. Design and methods: We investigated the effect of acute D 2 antagonism with metoclopramide on cortisol and ChA release from the adrenal gland by comparing the adrenal vein and infrarenal inferior vena cava (IVC) hormone levels at baseline and after metoclopramide administration in 34 consecutive patients undergoing AVS. Results: Metoclopramide increased plasma aldosterone in the IVC (P!0.00001) and in the adrenal vein blood (P!0.002) but failed to increase plasma cortisol concentration or ChA levels. Therefore, it did not increase the selectivity index based on the measurement of either hormone. Conclusions: This study shows that the release of cortisol and ChA is not subjected to tonic D 2 dopaminergic inhibition. Therefore, these findings lend no evidence for the usefulness of acute metoclopramide administration for enhancing the assessment of the selectivity of blood sampling during AVS with the use of either cortisol or ChA assay.

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“…SKF82958 produces doseresponsive effects on brain activity , but its effects on prolactin secretion are not well described. Pramipexole is a D 3 -preferring D 2 -like dopamine agonist (Mierau 1995;Mierau et al 1995;Piercey 1998) that produces regionally specific effects on brain activity (Black et al 2002) and reduces prolactin secretion in humans (Schilling et al 1992;Samuels et al 2006a). For both of these drugs there is strong evidence that they affect regional cerebral blood flow (rCBF) via changes in neuronal activity and not via direct vascular effects (Black et al , 2002.…”

Section: Introductionmentioning

confidence: 99%

Prolactin and fMRI response to SKF38393 in the baboon

Miller

Marks

Koller

et al. 2013

Preprint

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Background: This study's goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method.Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps ("time course studies") were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose-response curves. Methods:We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m.ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D 1 -like agonists SKF82958 and SKF38393 or the D 2 -like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928 -9.28 mg/kg, N=5 animals) or pramipexole (0.00928 -0.2 mg/kg, N=1) was given i.v. during a 40-minute blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 minutes after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED 50 (estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain. Results: Prolactin rose 2.4-to 12-fold with anesthesia alone, peaking around 50-90 minutes after ketamine administration and gradually tapering off but still remaining higher than baseline on isoflurane 3-5 hours after ketamine. Baseline prolactin level increased with age. SKF82958 0.1mg/kg i.v. produced no noticeable change in plasma prolactin concentration. SKF38393 produced a substantial increase in prolactin release that peaked at around 20-30 minutes and declined to pre-drug levels in about an hour. Pramipexole quickly reduced prolactin levels below baseline, reaching a nadir 2-3 hours after infusion. SKF38393 produced clear, dose-responsive BOLD signal changes, and across the four regions, ED 50 was estimated at 1.6-7.7mg/kg.Conclusions: In the baboon, the dopamine D 1 receptor agonist SKF38393 produces clear plasma prolactin and phMRI dose-response curves.Variability in age and a modest sample size limit the precision of the conclusions. PrePrints peaked at around 20-30 minutes and declined to pre-drug levels in about an hour. PeerJ PrePrintsPramipexole quickly reduced prolactin levels below baseline, reaching a nadir 2-3 hours after infusion. SKF38393 produced clear,...

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Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors

Cited by 233 publications

References 18 publications

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

Prolactin and fMRI response to SKF38393 in the baboon

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