Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pramipexole (PPX) is a D(2)/D(3) receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission.
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PMID:Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain. 1868 11

The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.
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PMID:Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. 1927 53

Treatment with pramipexole, a dopamine D(3)/D(2) receptor agonist, reduces depressive symptoms in patients suffering from Parkinson's disease. To test the putative antidepressant quality of pramipexole, its effects were assessed in one of the most attractive animal models of depression, the olfactory bulbectomized (OBX) rat. Two experiments studied the effects of pramipexole on bulbectomy-induced hyperactivity. In experiment I, pramipexole was tested at 0.3 and 1.0 mg/kg together with the reference dopamine D(3) receptor agonist 7-OH-DPAT (0.1 mg/kg) and the tri-cyclic antidepressant imipramine (10 mg/kg). In experiment II, pramipexole was tested at lower doses: 0.03 and 0.1 mg/kg, with the same reference compounds. All animals were tested in the open field on days one (acute), seven (sub-chronic) and fourteen (chronic) of administration, as well as one week after cessation of treatment. Pramipexole, in a U-shaped dose response, reduced bulbectomy-induced hyperactivity after (sub) chronic but not acute administration (like imipramine and 7-OH-DPAT). The highest dose of pramipexole (1.0 mg/kg) did not reduce OBX hyperactivity during treatment. However, one week after cessation of treatment, all pramipexole (including the 1.0 mg/kg dose), 7-OH-DPAT and imipramine groups showed a reduction in OBX-induced hyperactivity. Pramipexole and 7-OH-DPAT exert an antidepressant profile in the OBX-rat model in normalizing bulbectomy-induced hyperactivity during (sub) chronic treatment. Moreover, treatment with both these compounds induced long-lasting changes in the bulbectomized brain similar to established antidepressants, strongly predicting antidepressant activity in major depression.
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PMID:Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats. 1954 14

The open 3-month study of influence of D2/D3 dopamine agonist pramipexole on of Parkinson's disease (PD) features, which are relatively resistant to traditional dopaminergic therapy: tremor, affective and cognitive impairment, has been conducted. Ninety-eight patients with PD, aged from 42 to 75 years (mean age 63,2+/-10,2 years), have been included in the study. Twenty percents of patients included were older than 70 years. The Hoehn and Yahr stage varied from 1 to 4 (men stage 2,5+/-0,8). Seventy percents of patients received levodopa (mean dosage 351,2+/-279,4 mg); 62% had motor fluctuations and 43% - dyskinesias. Pramipexole was titrated to effective dose (maximum 3 mg/d, mean 2,1 mg/d). The decrease of resting tremor by 50% and postural and kinetic tremor (assessed with the UPDRS and spiralography) by 37% was noticed to the end of 3 month. The severity of depressive symptoms measured with the Montgomery-Asberg scale and a modified version of the Geriatric Depression scale was reduced by one third. The statistically significant decrease of motor fluctuations and dyskinesias, increase of verbal fluency (but not other cognitive functions) were also found. The clinically significant effect of reducing of motor and non-motor symptoms was seen in 86% patients regardless of their age, illness duration, severity of motor deficit and affective and cognitive disturbances. The fair tolerability of the drug was shown including patients older than 70 years.
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PMID:[Influence of dopamine agonist pramipexole (mirapex) on tremor, cognitive and affective impairment in patients with Parkinson's disease]. 1973 67

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52+/-0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.
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PMID:Compulsive habits in restless legs syndrome patients under dopaminergic treatment. 1996 9

The open 6-month study (the MIRAG study) on the effect of D2/D3 dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease (PD) was carried out. Ninety-eight patients, aged from 42 to 75 years (mean age 63.2+/-10.2 years) were included in the study. Scores on the Hoehn and Yahr scale varied from 1 to 4 (mean 2,5+/-0,8). Seventy percent of patients received levodopa in average dose 351.2+/-279.4 mg; 62% of patients had motor fluctuations and 43% had dyskinesias. Pramipexole was titrated to the effective dose (maximum 3 mg/d, mean 2.1 mg/d). In the end of the study, resting tremor was reduced by 54%, postural and kinetic tremor, as assessed with UPDRS and spirography, by 50% and 15%, respectively. The severity of depressive symptoms measured with the Montgomery-Asberg Scale and a modified version of the Geriatric-Depression Scale (GDS-15) was reduced by 56%. Motor fluctuations and dyskinesias were significantly reduced while cognitive functions were not changed. The clinically significant effect reflected in the reduction of motor and non-motor symptoms was observed in 83% of patients, regardless of disease duration, severity of motor deficit, affective and cognitive disorders,. The drug was well tolerated in all patients, including those older than 70 years. Pramipexole improved quality of life in PD patients due to the attenuation of cardinal motor parkinsonian symptoms as well as symptoms, which were relatively resistant to levadopa, e.g. postural and kinetic tremor, and depression. The therapeutic effect remained for at least 6 months.
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PMID:[Effect of dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease]. 2043 48

Perhaps the most important unmet need in Parkinson's disease (PD) is the ability to slow or prevent progression of the neurodegeneration that underlies the motor and nonmotor features of this disorder. Pramipexole, a dopamine agonist used for the symptomatic treatment of PD, has demonstrated neuroprotective properties in laboratory studies. The PRamipexole On Underlying Disease (PROUD) study is a randomized, double-blind clinical trial evaluating the ability of pramipexole to modify disease progression using a delayed-start design. PD patients (n = 535) with mean age 62.5 years, mean duration since diagnosis of 4.4 months, and mean total Unified Parkinson's disease Rating Scale (UPDRS) score of 24.5 were recruited. In Phase I, patients were randomly assigned to be titrated to 1.5 mg pramipexole or placebo and maintained on study drug for 6-9 months. In Phase II, all patients were titrated to 1.5 mg pramipexole and maintained on study drug until the end of the study at 15 months. No rescue medication was allowed in the protocol. The primary endpoint is the change in total UPDRS score (parts I-III) from baseline to 15 months. A range of secondary endpoints separately assess UPDRS subscales, quality of life, depression, and impulse control disorders. A sub-study examined dopamine transporter uptake scans at baseline and 15 months. The results of PROUD will provide insight into the potential for early versus delayed treatment with pramipexole to modify motor outcome at 15 months in recently diagnosed PD patients.
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PMID:Rationale for delayed-start study of pramipexole in Parkinson's disease: the PROUD study. 2054 10

The non-ergot dopamine agonist pramipexole is currently indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and for the treatment of moderate-to-severe primary restless legs syndrome. A new extended-release formulation of pramipexole has now also been launched in Europe and the US to improve ease of use, compliance and provide a more continuous therapeutic effect over 24 hours. Before initiating any treatment, the benefit-risk ratio to the individual patient must be considered. For pramipexole in the treatment of Parkinson's disease, this means taking into account the available evidence regarding its symptomatic efficacy, effect on delaying long-term levodopa-related motor complications, beneficial effect on non-motor symptoms such as depression, and its safety and tolerability profile. Studies have shown that pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Trials further suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to the amelioration of depressive symptoms in Parkinson's disease. Pramipexole is generally well tolerated; however, compared with levodopa treatment, pramipexole is associated with a higher rate of some dopaminergic adverse effects.
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PMID:Role of pramipexole in the management of Parkinson's disease. 2083 95

Comorbid depressive and anxiety disorders are associated with chronic physical illnesses. Treatment with antidepressants and mood stabilizers require knowledge about toxicity, potential side effects, and drug interactions. According to controlled studies in comorbid cardiovascular diseases, diabetes mellitus, and cerebrovascular disorders (post-stroke depression), serotonin-selective reuptake inhibitors (SSRIs), e.g., sertraline and citalopram, are preferred. Pramipexole, reboxetine, mirtazapine, or nortriptyline showed efficacy in treatment of Parkinson depression. Chronic pain syndromes can be improved with low-dose tricyclic antidepressants. Both establishment of compliance and follow-up examinations are essential. Combined treatment with psychotherapeutic interventions, including coping strategies, should be used whenever possible.
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PMID:[Possibilities and limitations of psychopharmacological treatments in patients with psychological comorbidity]. 2124 27

Depression is a common occurrence in patients with Parkinson's disease (PD). Pramipexole is a dopamine agonist that has been used to treat both motor and non-motor symptoms associated with PD. We conducted a study to elucidate the effect of pramipexole on each of the depressive symptoms as assessed by the Zung Self-Rating Depression Scale (SDS). Twenty patients with PD were treated with pramipexole 1.5-3.0 mg daily for 2-3 months. The SDS and the Unified Parkinson Disease Rating Score (UPDRS) were measured in each subject before and after the treatment. Both the SDS and the UPDRS decreased significantly after treatment with pramipexole. Individual assessment of each item in the SDS indicated that "crying spell", "confusion", "psychomotor retardation", "emptiness", and "dissatisfaction" symptoms improved significantly following treatment, while "depressed affect", "decreased libido", "constipation", and "indecisiveness" symptoms were worse after the treatment. As the symptom of "indecisiveness" did not respond to treatment, it might be an essential symptom in patients with PD.
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PMID:The effect of pramipexole on depressive symptoms in Parkinson's disease. 2193 69


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