Disease relevance of pramipexole

• METHODS: In this 14-week, single-center, double-blind, placebo-controlled, parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening [1].
• The most common adverse events associated with pramipexole were transient anxiety and weight loss [1].
• Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells [2].
• In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients [3].
• Pramipexole in progressive supranuclear palsy [4].

Psychiatry related information on pramipexole

• Pramipexole in refractory bipolar depression [5].
• Pramipexole augmentation in panic with agoraphobia [6].
• Encouraging initial response of restless legs syndrome to pramipexole [7].
• Locomotor activity was also assessed following pramipexole administration [8].
• There is very low evidence for the treatment of other problems: "possibly useful" drugs are L-dopa and pramipexole for rigidity; amitryptiline and mirtazapine for depression; risperidone for psychosis; and olanzapine, haloperidol, and buspirone for behavioral symptoms in HD [9].

High impact information on pramipexole

• After 3-4 h of infusion, when the expected natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the kidneys were removed for analysis of PLC isoform protein expression activity [10].
• Other criticisms include insufficient data on the use of the potential neuroprotectant selegiline and patients on pramipexole in the SPECT study appear to have been clinically slow progressors [11].
• At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance) [12].
• A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications [1].
• We also found that the agonist pramipexole failed to stimulate activation of Akt in PC12-D2R cells, providing an explanation for our previous observations that, despite efficiently activating G-protein signaling, this agonist had little cytoprotective activity in this experimental system [13].

Chemical compound and disease context of pramipexole

• The pooled RR (for pramipexole and ropinirole combined) of hallucinations was 1.92 (95% CI 1.08-3.43) when compared with levodopa [14].
• Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss [15].
• Repeated administration of talipexole or pramipexole may have neuroprotective effect in neurodegenerative disorders [16].
• Pramipexole versus sertraline in the treatment of depression in Parkinson's disease : A national multicenter parallel-group randomized study [17].
• The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg) [18].

Biological context of pramipexole

• Similarly, pramipexole pretreatment increased Bcl-2 and inhibited MPP+-induced apoptosis [2].
• The authors studied the pharmacokinetics of levodopa (LD) with and without pramipexole (PPX) in men and postmenopausal women with PD [19].
• Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication [3].
• Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms [20].
• The proportion of high affinity binding sites recognized by S32504, pramipexole and ropinirole in membranes derived from cells co-expressing D3 and D2L sites was higher than in an equivalent mixture of membranes from cells expressing D3 or D2L sites, consistent with the promotion of heterodimer formation [21].

Anatomical context of pramipexole

• Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low-dose MPTP treatment designed to induce a partial lesion of the substantia nigra [22].
• However, pramipexole reduced caspase-3 activation, decreased the release of cytochrome c and prevented the fall in the mitochondrial membrane potential induced by MPP+ and rotenone [20].
• To test if the D(3) receptor preferring agonists S32504 and pramipexole act through D(2) or D(3) receptors and via brain-derived neurotrophic factor (BDNF)-dependent pathways, we utilized a terminally differentiated neuroblastoma SH-SY5Y cell line exhibiting a dopaminergic phenotype [23].
• Pramipexole protects against H(2)O(2)-induced PC12 cell death [24].
• Pramipexole also reduced reserpine-enhanced tonic and reflex EMG activities in the gastrocnemius muscle [25].

Associations of pramipexole with other chemical compounds

• Two centers tested a new dopamine agonist, pramipexole, in 23 patients with RLS in a time-limited, open-label, clinical trial [7].
• Falling asleep at the wheel: motor vehicle mishaps in people taking pramipexole and ropinirole [26].
• The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist, on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels were investigated in a randomized, double-blind, crossover study in 12 healthy volunteers [27].
• Stereoisomers of pramipexole (PPX), a free radical scavenger and inhibitor of MTP opening, inhibited caspase activation (MPP(+) and BA) and restored calcein accumulation (MPP(+)) [28].
• Dopamine autoreceptor agonists like pramipexole, roxindole, talipexole and OPC-4392 as well as partial agonists like terguride and SDZ HDC 912 have been tested in positive schizophrenic symptomatology in order to reduce the postulated excess of central dopaminergic activity [29].

Gene context of pramipexole

• Pramipexole decreased serum prolactin levels in a dose-dependent manner, with a maximum effect after 2 to 4 hours [27].
• CONCLUSIONS: Taken together, these studies suggest that the D2 receptor rather than the D3 receptor is important for the antidepressant-like activity observed for pramipexole in the mouse forced swim test [8].
• Antibody directed against BDNF concentration-dependently blocked both the neuroprotective effects of BDNF and those of pramipexole and S32504 against MPP(+) [23].
• Talipexole and pramipexole at low concentration (0.1-1 mM) significantly inhibited the accumulation of cytochrome c or alpha-synuclein in the cytosolic fraction [30].
• In the present study, we examined the effects of talipexole and pramipexole on the release of cytochrome c and alpha-synuclein, their aggregations, and activation of caspases [30].

Analytical, diagnostic and therapeutic context of pramipexole

• CONCLUSION: In a subset of patients with fibromyalgia, approximately 50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated [1].
• Thirty clinically asymmetrical patients were randomly assigned to receive 6 weeks of L-dopa (300/75 mg/d), pramipexole (1.5 mg/d), or placebo; PET studies were performed before and after treatment [31].
• A double-blind, randomized, multicenter study was performed to compare the safety, tolerance, and efficacy of pramipexole versus placebo in patients with advanced PD with motor fluctuations [32].
• Because of concern regarding driving safety, we evaluated the incidence and nature of somnolence experienced by patients receiving pramipexole in clinical trials at our center [33].
• Plasma and urine samples collected within the four dose intervals were assayed for concentrations of pramipexole, using high-performance liquid chromatography [34].

References