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Sporn, Jonathan; Ghaemi, S. Nassir; Sambur, Marnie R.; Rankin, Meridith A.; Recht, James; Sachs, Gary S.; Rosenbaum, Jerrold F.; Fava, Maurizio

doi:10.1023/a:1009060800999

Cited by 49 publications

(12 citation statements)

References 9 publications

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“…119, 120, 121, 122, 123, 124, 125, 126, 127 Although there have not been any RCTs investigating the efficacy of methylphenidate or amphetamines in bipolar depression, the available open-label and naturalistic studies point towards a benefit of stimulants in a selected group of patients with drowsiness and fatigue. 128, 129, 130, 131 Randomised controlled studies and open-label reports with other stimulant like agents such as modafinil and its R-enantiomer, armodafinil also indicate efficacy in bipolar depression although the development programme for armodafinil failed.…”

Section: Modulation Of the Dopamine System And Treatment Of Bipolar Dmentioning

confidence: 99%

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

et al. 2017

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Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder. Converging findings from pharmacological and imaging studies support the hypothesis that a state of hyperdopaminergia, specifically elevations in D2/3 receptor availability and a hyperactive reward processing network, underlies mania. In bipolar depression imaging studies show increased dopamine transporter levels, but changes in other aspects of dopaminergic function are inconsistent. Puzzlingly, pharmacological evidence shows that both dopamine agonists and antidopaminergics can improve bipolar depressive symptoms and perhaps actions at other receptors may reconcile these findings. Tentatively, this evidence suggests a model where an elevation in striatal D2/3 receptor availability would lead to increased dopaminergic neurotransmission and mania, whilst increased striatal dopamine transporter (DAT) levels would lead to reduced dopaminergic function and depression. Thus, it can be speculated that a failure of dopamine receptor and transporter homoeostasis might underlie the pathophysiology of this disorder. The limitations of this model include its reliance on pharmacological evidence, as these studies could potentially affect other monoamines, and the scarcity of imaging evidence on dopaminergic function. This model, if confirmed, has implications for developing new treatment strategies such as reducing the dopamine synthesis and/or release in mania and DAT blockade in bipolar depression.

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Section: Modulation Of the Dopamine System And Treatment Of Bipolar Dmentioning

confidence: 99%

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

et al. 2017

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“…It was introduced for treating motor symptoms in patients with idiopathic Parkinson's disease (PD) [1] and has been shown to be effective by various clinical trials [2], [3]. In addition, various studies have recently found antidepressive effects of pramipexole not only in patients with PD complicated by depressive state [4], [5], [6], [7], but also in depressive patients without parkinsonian symptoms [8], [9], [10], [11], [12], [13], [14], [15], [16]. Its antidepressive effects have been also shown in animal experiments [17], [18].…”

Section: Introductionmentioning

confidence: 99%

Binding of Pramipexole to Extrastriatal Dopamine D2/D3 Receptors in the Human Brain: A Positron Emission Tomography Study Using 11C-FLB 457

et al. 2011

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The purpose of this study was to determine the binding sites of pramipexole in extrastriatal dopaminergic regions because its antidepressive effects have been speculated to occur by activating the dopamine D2 receptor subfamily in extrastriatal areas. Dynamic positron emission tomography (PET) scanning using 11C-FLB 457 for quantification of D2/D3 receptor subtype was performed on 15 healthy volunteers. Each subject underwent two PET scans before and after receiving a single dose of pramipexole (0, 0.125, or 0.25 mg). The study demonstrated that pramipexole significantly binds to D2/D3 receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus at a dose of 0.25 mg. These regions have been indicated to have some relation to depression and may be part of the target sites where pramipexole exerts its antidepressive effects.

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“…25 , 26 Moreover, Pramipexole, a D3 preferring agonist, was found to be effective in both unipolar and bipolar depression. 27 …”

Section: Introductionmentioning

confidence: 99%

Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Synthesis, biological characterization, and development of a pharmacophore model

Santra

Debnath

et al. 2014

Bioorganic & Medicinal Chemistry

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In this study we have generated a pharmacophore model of triple uptake inhibitor compounds based on novel asymmetric pyran derivatives and the newly developed asymmetric furan derivatives. The model revealed features important for inhibitors to exhibit a balanced activity against dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). In particular, a ‘folded’ conformation was found common to the active pyran compounds in the training set and was crucial to triple uptake inhibitory activity. Furthermore, the distances between the benzhydryl moiety and the N-benzyl group as well as the orientation of the secondary nitrogen were also important for TUI activity. We have validated our findings by synthesizing and testing novel asymmetric pyran analogs. The present work has also resulted in the discovery of a new series of asymmetric tetrahydrofuran derivatives as novel TUIs. Lead compounds 41 and 42 exhibited moderate TUI activity. Interestingly, the highest TUI activity by lead tetrahydrofuran compounds e.g. 41 and 42, was exhibited in a stereochemical preference similar to pyran TUI e.g. D-161.

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Cited by 49 publications

References 9 publications

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

Binding of Pramipexole to Extrastriatal Dopamine D2/D3 Receptors in the Human Brain: A Positron Emission Tomography Study Using 11C-FLB 457

Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Synthesis, biological characterization, and development of a pharmacophore model

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