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Concept: Dopamine agonists

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Background:  Although there are clinical reports of hair loss associated with levodopa and dopamine agonists, it is unclear whether dopamine exerts any direct effects on the human hair follicle (HF). Objectives:  Given the widespread use of dopamine agonists and antagonists in clinical medicine, we sought to determine whether dopamine exerts direct effects on human HF growth and pigmentation in vitro, and whether human HFs express dopamine receptors (DRs). Methods:  Microdissected human scalp HFs from women were treated in serum-free organ culture for 7 days with dopamine (10-1000 nmol L(-1) ), and the effects on hair shaft production, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and apoptosis, and HF pigmentation were measured by quantitative (immuno)histomorphometry. Results:  Dopamine had no consistent effect on hair shaft production, but did promote HF regression (catagen). It was also associated with significantly reduced proliferation of HF matrix keratinocytes (P < 0.01) and reduced intrafollicular melanin production. Dopamine receptor transcripts were identified in HFs and skin. Conclusions:  These data provide evidence that dopamine is an inhibitor of human hair growth, via the promotion of catagen induction, at least in vitro. This may offer a rational explanation for the induction of telogen effluvium in some women treated with dopamine agonists such as bromocriptine. Moreover, dopaminergic agonists deserve further exploration as novel inhibitors of unwanted human hair growth (hirsutism, hypertrichosis).

Concepts: Skin, Dopamine receptor, Dopamine, Hair, Hair follicle, Facial hair, Dopamine agonists, Dopamine agonist

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This mixed treatment comparison is used to compare the adverse effects of eleven different drugs used to treat Parkinson’s disease (PD). The drugs that we compare include the following: ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil, pergolide, and levodopa.

Concepts: Parkinson's disease, Dopamine, Pramipexole, Ropinirole, Cabergoline, Dopamine agonists, Dopamine agonist, Piribedil

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A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson’s disease (PD).

Concepts: Parkinson's disease, Dopamine, Pramipexole, Ropinirole, Carbidopa, Dopamine agonists, Dopamine agonist, Piribedil

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Dopamine acts through dopamine Type I receptors (comprising D1 and D5 subtypes) and dopamine Type II receptors (comprising D2, D3, and D4 subtypes). Intracranial self-stimulation (ICSS) is 1 experimental procedure that can be used to evaluate abuse-related effects of drugs targeting dopamine receptors. This study evaluated effects of dopamine receptor ligands on ICSS in rats using experimental procedures that have been used previously to examine abused indirect dopamine agonists such as cocaine and amphetamine. Male Sprague-Dawley rats responded under a fixed-ratio 1 schedule for electrical stimulation of the medial forebrain bundle, and frequency of stimulation varied from 56-158 Hz in 0.05 log increments during each experimental session. Drug potency and time course were determined for the D1 ligands A77636, SKF82958, SKF38393, fenoldopam, and SCH39166 and the D2/3 ligands sumanirole, apomorphine, quinpirole, PD128907, pramipexole, aripiprazole, eticlopride, and PG01037. The high-efficacy D1 agonists A77636 and SKF82958 produced dose-dependent, time-dependent, and abuse-related facilitation of ICSS. Lower efficacy D1 ligands and all D2/3 ligands failed to facilitate ICSS at any dose or pretreatment time. A mixture of SKF82958 and quinpirole produced a mixture of effects produced by each drug alone. Quinpirole also failed to facilitate ICSS after regimens of repeated treatment with either quinpirole or cocaine. These studies provide more evidence for divergent effects of dopamine D1- and D2-family agonists on ICSS procedure in rats and suggest that ICSS may be a useful complement to other approaches for preclinical abuse potential assessment, in part because of the reproducibility of results. (PsycINFO Database Record

Concepts: Dopamine receptor, Agonist, Dopamine receptor D3, Dopamine, Amphetamine, Dopamine receptor D1, Dopamine receptor D2, Dopamine agonists

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Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson’s disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans.

Concepts: Parkinson's disease, Substantia nigra, Dopamine, Pramipexole, Ropinirole, Restless legs syndrome, Dopamine agonists, Dopamine agonist

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In treating Parkinson’s disease with dopaminergic agonists, such as pramipexole, ropinirole, pergolide, rotigotine, apomorphine or bromocriptine, it has been observed that a significant number of patients develop Impulse-Control Disorders such as compulsive shopping, pathological gambling, or hypersexuality. Because the dopamine agonists have high affinities for the dopamine D2 and D3 receptors, the drug dissociation constants of these drugs at the functional high-affinity states of these receptors, namely D2High and D3 high, were compared. The data show that, compared to the other dopamine agonist drugs, pramipexole has a relatively high selectivity for the dopamine D3 receptor, as compared to D2, suggesting that the D3 receptor may be a primary target for pramipexole. There is a trend showing that the proportion of Impulse-Control Disorders is related to the selectivity for D3 receptors over D2 receptors, with pramipexole having the highest association with, or frequency of, Impulse-Control disorders. While the number of studies are limited, the proportion of patients with Impulse-Control Disorder in Parkinson patients treated with an add-on agonist were 32% for pramipexole, 25% for ropinirole, 16% for pergolide, 22% for rotigotine, 10% for apomorphine, and 6.8% for bromocriptine. Clinically, temporary replacement of pramipexole by bromocriptine may provide relief or reversal of the impulsive behaviour associated with selective D3 stimulation by either pramipexole or ropinirole, while maintaining D2 stimulation needed for the anti-Parkinson action. This article is protected by copyright. All rights reserved.

Concepts: Parkinson's disease, Dopamine receptor, Pramipexole, Ropinirole, Cabergoline, Restless legs syndrome, Dopamine agonists, Dopamine agonist

0

We examined the effects of two dopamine agonists, cabergoline and rotigotine, on tacrine-induced tremor and c-Fos expression in rats.

Concepts: Parkinson's disease, Prolactinoma, Pramipexole, Cabergoline, Restless legs syndrome, Dopamine agonists, Dopamine agonist, Rotigotine

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The aim of this study was to investigate the effects of piribedil on vigilance and cognitive performance in patients with Parkinson disease experiencing excessive daytime sleepiness on pramipexole or ropinirole.

Concepts: Parkinson's disease, Dopamine, Pramipexole, Ropinirole, Restless legs syndrome, Dopamine agonists, Dopamine agonist, Piribedil

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Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson’s disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical practice.

Concepts: Parkinson's disease, Dopamine, Pramipexole, Ropinirole, Restless legs syndrome, Dopamine agonists, Dopamine agonist, Rotigotine

0

Restless legs syndrome (RLS) is related to parity, and its symptoms may worsen during pregnancy. Treatment with levodopa or dopamine agonists is the first-line therapy for RLS; however, there are limited data on treatment in pregnancy. We therefore assessed the safety of levodopa, pramipexole, rotigotine, and ropinirole in pregnancy.

Concepts: Parkinson's disease, Dopamine, Pramipexole, Ropinirole, Restless legs syndrome, Dopamine agonists, Dopamine agonist, Rotigotine