- Quantitative Comparison of the Efficacies of 5 First-Line Drugs for Primary Restless Leg Syndrome. [Journal Article]
- JCJ Clin Pharmacol 2019 May 20
- Comparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restle…
Comparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restless leg syndrome (RLS) are lacking because of the few head-to-head clinical trials. A model-based meta-analysis approach was employed to quantitatively compare the efficacies of these 5 first-line RLS drugs. Longitudinal efficacy data of RLS drugs were collected from published eligible literature. Mean changes in both the International Restless Leg Syndrome Study Group (IRLS) rating scale and Clinical Global Impression Improvement (CGI-I) scale response rate were analyzed. A study-level population pharmacodynamic model was used to fit the dose-effect relationship and to describe the therapeutic effect over time for RLS drugs and placebo, and the typical efficacies of these drugs were compared. The onset of action was rapid for RLS drugs. In the placebo group, typical maximum IRLS reduction (Emax,IRLS) and CGI-I response rate (Emax,CGI-I) were -9.34 points and 48.2%, respectively. After deducting placebo effects, we found that the baseline IRLS score was significantly correlated with the Emax,IRLS of dopaminergic agonists. Typical Emax,IRLS of dopaminergic agonists was expressed as - 7.7 - 0.682 × (baseline IRLS score - 24) points. Typical Emax,IRLS values of pregabalin and gabapentin enacarbil were -5.95 points and -4.00 points, respectively. The therapeutic effect of dopaminergic agonists was found to be associated with baseline symptom severity. In RLS patients with more severe symptoms, the therapeutic effect of dopaminergic agonists tended to be better than that of α-2-δ ligands.
- Indirect Comparison of Ropinirole and Pramipexole as Levodopa Adjunctive Therapy in Advanced Parkinson's Disease: A Systematic Review and Network Meta-Analysis. [Review]
- ATAdv Ther 2019; 36(6):1252-1265
- CONCLUSIONS: Adjunctive therapy with ropinirole-SR or pramipexole appears to offer similar efficacy and tolerability in patients with advanced PD on the basis of this indirect comparison.
- Corneal Edema Associated With Systemic Dopaminergic Agents. [Journal Article]
- CCornea 2019 Apr 02
- CONCLUSIONS: Methylphenidate, ropinirole, and resiniferatoxin have different mechanisms of actions but have a common end point leading to increased dopamine. We believe that these agents are linked with the reversible corneal edema seen in our 3 patients. This strongly correlates with previous studies that have linked amantadine, a drug that blocks dopamine reuptake, to reversible corneal edema.
- Direct Drug Delivery of Low-Permeable Compounds to the Central Nervous System Via Intranasal Administration in Rats and Monkeys. [Journal Article]
- PRPharm Res 2019 Apr 01; 36(5):76
- CONCLUSIONS: Compound permeability is a key determinant of Kp increase by intranasal administration. This route of administration is more beneficial for low-permeable compounds and enhances their delivery to the brain in rodents and non-human primates.
- Takotsubo cardiomyopathy associated with serotonin syndrome in a patient with stroke: A case report. [Case Reports]
- MMedicine (Baltimore) 2019; 98(13):e15057
- CONCLUSIONS: Prognosis of TC is usually favorable; however, it could be fatal in some cases. Clinicians should be aware of the potential development of TC in patients with stroke presenting with SS following the administration of serotonergic and dopaminergic agents.
- Effectiveness of Integrative Therapy for Parkinson's Disease Management. [Journal Article]
- FAFront Aging Neurosci 2019; 11:40
- CONCLUSIONS: It has not been clearly identified that integrative therapy with KM and biomedicine for PD management is better treatment for patients compared to biomedicine monotherapy; however, we found a clue of better result in integrated therapy. Therefore, further investigation by increasing the number of subjects is needed to confirm the findings presented herein.
- Creativity related to dopaminergic treatment: A multicenter study. [Journal Article]
- PRParkinsonism Relat Disord 2019 Feb 22
- Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). …
Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). However, patients with Parkinson's disease (PD) may experience enhanced creativity during DA therapy, often manifesting as newfound artistic pursuits. Though ICD is very well recognized in the literature, enhanced creativity remains underreported, probably because, unlike ICD, enhanced creativity is often positive and rarely disruptive for patients and relatives. We studied 21 patients (20 patients with PD and one patient with restless-legs syndrome) with enhanced creativity. These individuals engaged in artistic activities after dopaminergic treatment; all but one were treated with DA (pramipexole, 14/21; ropinirole, 4/21; rotigotine 2/21). Most patients preferred painting as their main activity, but many were engaged in several activities, usually in combination. We hypothesize that by facilitating a stimulating environment for parkinsonian patients, this positive phenomenon may present more frequently.
- The novel hybrid agonist HyNDA-1 targets the D3R-nAChR heteromeric complex in dopaminergic neurons. [Journal Article]
- BPBiochem Pharmacol 2019; 163:154-168
- In this paper, we designed, synthesized and tested a small set of three new derivatives potentially targeting the D3R-nAChR heteromer, a receptor complex recently identified and characterized as the …
In this paper, we designed, synthesized and tested a small set of three new derivatives potentially targeting the D3R-nAChR heteromer, a receptor complex recently identified and characterized as the molecular entity that, in dopaminergic neurons, mediates the neurotrophic effects of nicotine. By means of a partially rigidified spacer of variable length, we incorporated in the new compounds (1a-c) the pharmacophoric substructure of a known β2-subunit-containing nAChR agonist (A-84543) and that of the D2/D3R agonist drug ropinirole. All the compounds retained the ability to bind with high affinity both β2-subunit-containing nAChR and D3R. Compound 1a, renamed HyNDA-1, which is characterized by the shortest linker moiety, was the most interesting ligand. We found, in fact, that HyNDA-1 significantly modulated structural plasticity on both mice and human dopaminergic neurons, an effect strongly prevented by co-incubating this ligand with either nAChR or D3R antagonists. Moreover, the neurotrophic effects of HyNDA-1 were specifically lost by disrupting the complex with specific interfering peptides. Interestingly, by using the Bioluminescence Resonance Energy Transfer 2 (BRET2) assay in HEK-293 transfected cells, we also found that HyNDA-1 has the ability to increase the affinity of interaction between nAChR and D3R. Overall, our results indicate that the neurotrophic effects of HyNDA-1 are mediated by activation of the D3R-nAChR heteromeric complex specifically expressed on dopaminergic neurons.
- Increased motor impulsivity in a rat gambling task during chronic ropinirole treatment: potentiation by win-paired audiovisual cues. [Journal Article]
- PPsychopharmacology (Berl) 2019 Jan 31
- CONCLUSIONS: These data suggest that explicitly signaling loss prevents the increase in preference for uncertain rewards caused by D2/3 receptor agonists observed previously. The ability of win-paired cues to amplify ropinirole-induced increases in motor impulsivity may explain why compulsive use of EGMs is particularly common in iGD. These data offer valuable insight into the cognitive-behavioral mechanisms through which chronic dopamine agonist treatments may induce iGD and related impulse control disorders.
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- Drugs-Induced Pathological Gambling: An Analysis of Italian Spontaneous Reporting System. [Journal Article]
- JGJ Gambl Stud 2019 Jan 23
- Pathological gambling has been reported as a direct complication of Parkinson's disease and its pharmacological treatment based on dopamine agonists. Moreover, further medications (not dopamine agoni…
Pathological gambling has been reported as a direct complication of Parkinson's disease and its pharmacological treatment based on dopamine agonists. Moreover, further medications (not dopamine agonists) were associated to the occurrence of gambling disorder. We aim to analyze the spontaneous reports of gambling disorder on the whole Italian territory with a focus on Campania Region (Southern Italy) from January 1st 2002 to July 31st 2018. We analyzed gambling disorder's reports across the 2002-2018 period in the Italian spontaneous reporting database (Rete Nazionale di Farmacovigilanza-RNF), with a focus on Campania region. 94 suspected cases of gambling disorder associated to apomorphine, aripiprazole, cabergoline, levodopa, levodopa and derivatives in association with entacapone/benserazide and carbidopa, pergolide, pramipexole, ropinirole, and rotigotine were reported into the RNF. Of these cases, two related to pramipexole and one to aripiprazole were sent to Campania Pharmacovigilance Regional Centre. Although it is widely recognized that dopamine agonists may induce behavioral disorders, Parkinson's disease is itself associated to pathological gambling, compulsive shopping and eating. Since our results could not clarify the correlation between Parkinson's disease, its pharmacological treatment and pathological gambling, in order to better define this correlation there is a need to conduct further ad hoc observational studies.