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[PMID]:28842205
[Au] Autor:Jean PA; Sloter ED; Plotzke KP
[Ad] Endereço:Dow Corning Corporation, Midland, MI, 48686, United States. Electronic address: pajean4@gmail.com.
[Ti] Título:Effects of chronic exposure to octamethylcyclotetrasiloxane and decamethylcyclopentasiloxane in the aging female Fischer 344 rat.
[So] Source:Toxicol Lett;279 Suppl 1:54-74, 2017 Oct 20.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are used as intermediates or monomers in the synthesis of silicon-based polymers for industrial or consumer applications. D4 and D5 may remain as residual monomer in these polymers at less than 1000ppm and may therefore be present as a minor impurity in consumer products. For D5, in addition to the manufacture of polymers, its uses include intentional addition to consumer products, personal care products and some dry- cleaning solvents. Two-year rodent chronic bioassays were conducted with both substances and borderline increases in the incidence of uterine tumors were observed, specifically, benign uterine adenoma with D4 and adenocarcinoma with D5. The effects profile and induction of uterine tumors share some similarity with that seen with chronic exposure to dopamine agonists. The current study investigated the potential for D4 and D5 to elicit dopamine agonist-like effects on estrous cyclicity. Separate groups of reproductively senescent female Fischer 344 rats (F344) were exposed via vapor inhalation to D4 (700ppm, 9.3mg/L) or D5 (160ppm, 2.1mg/L) or to a diet containing 0.0045, 0.045, or 4.5ppm pergolide mesylate (PM), a potent dopamine agonist used here as a reference substance, from 11 through 24 months of age. The primary focus was to characterize the effects of D4 and D5 exposure on estrous cyclicity relative to that observed with PM. As a monitoring effort, circulating endogenous estradiol, progesterone, prolactin and corticosterone levels were evaluated monthly. A blood sample from each rat was obtained via tail vein in the afternoon after the daily inhalation exposure period once every 4 weeks. Histomorphologic examination of the major organs including the reproductive tract was conducted on all animals at study termination. This study has shown that chronic exposure to D4 and D5 can affect cyclicity in the reproductively senescent F344 rat. For each substance the effect on cyclicity involved reduction in the incidence of pseudopregnancy with a shift toward cycles more typical of younger animals. D4 and D5 induced an increase in estrous cycle repetition whereas D4 also increased the incidence of extended estrus. These shifts resulted in animals entering proestrus/estrus significantly more times over the duration of the study than seen in the control group. Similar effects were observed with the reference substance, PM. However, distinct differences in the timing and magnitude of the effects on the estrous cycle and impact on prolactin, progesterone, estradiol, and corticosterone suggest that D4 and D5 are not classical dopamine agonists even though a similar increased incidence of proestrus/estrus was also observed with PM. These results may prove important with respect to understanding D4- and D5-induced uterine tumor response in the F344 rat, given the relationship between increased incidence of uterine endometrium stimulation by endogenous estrogen as a consequence of extended or more frequent proestrus/estrus, uterine tumor risk, and questions of relevance to humans. Recent publications have summarized the existing data on D4 and D5, with emphasis on exploring the biological relevance of the uterine tumors (Klaunig et al., 2016a,b; Franzen et al., 2017; Dekant and Klaunig, 2016; Dekant et al., 2017). The authors concluded that although the mode of action has not yet been fully established, the data, including the findings from this study, indicate that the D4- and D5-induced uterine tumors observed in the rodent chronic bioassays have no relevance for human risk characterization based not only on the distinct species differences in regulation of the reproductive systems, but also the high exposure levels and duration required for expression in rats.
[Mh] Termos MeSH primário: Siloxanas/toxicidade
[Mh] Termos MeSH secundário: Envelhecimento
Ração Animal/análise
Animais
Dieta/veterinária
Esquema de Medicação
Ciclo Estral
Feminino
Exposição por Inalação
Pergolida/administração & dosagem
Ratos
Ratos Endogâmicos F344
Siloxanas/administração & dosagem
Siloxanas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Siloxanes); 0THT5PCI0R (decamethylcyclopentasiloxane); 24MJ822NZ9 (Pergolide); CZ227117JE (octamethylcyclotetrasiloxane)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE


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[PMID]:28190613
[Au] Autor:Durham AE
[Ad] Endereço:Liphook Equine Hospital, Liphook, Hampshire GU30 7JG, UK. Electronic address: andy.durham@theleh.co.uk.
[Ti] Título:Therapeutics for Equine Endocrine Disorders.
[So] Source:Vet Clin North Am Equine Pract;33(1):127-139, 2017 Apr.
[Is] ISSN:1558-4224
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency.
[Mh] Termos MeSH primário: Doenças do Sistema Endócrino/veterinária
Doenças dos Cavalos/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Agonistas de Dopamina/uso terapêutico
Doenças do Sistema Endócrino/tratamento farmacológico
Cavalos
Pergolida/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Dopamine Agonists); 24MJ822NZ9 (Pergolide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170602
[Lr] Data última revisão:
170602
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE


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[PMID]:27301465
[Au] Autor:McFarlane D; Banse H; Knych HK; Maxwell LK
[Ad] Endereço:Center for Veterinary Health Sciences, Physiological Sciences, Oklahoma State University, Stillwater, OK, USA.
[Ti] Título:Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.
[So] Source:J Vet Pharmacol Ther;40(2):158-164, 2017 Apr.
[Is] ISSN:1365-2885
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.
[Mh] Termos MeSH primário: Doenças dos Cavalos/tratamento farmacológico
Pergolida/farmacocinética
Doenças da Hipófise/veterinária
Adeno-Hipófise Parte Intermédia/patologia
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/sangue
Hormônio Adrenocorticotrópico/metabolismo
Animais
Área Sob a Curva
Meia-Vida
Cavalos
Pergolida/administração & dosagem
Pergolida/uso terapêutico
Doenças da Hipófise/tratamento farmacológico
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
24MJ822NZ9 (Pergolide); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160616
[St] Status:MEDLINE
[do] DOI:10.1111/jvp.12339


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[PMID]:27488420
[Au] Autor:Reichelt D; Radad K; Moldzio R; Rausch WD; Reichmann H; Gille G
[Ti] Título:Comparable Neuroprotective Effects of Pergolide and Pramipexole on Ferrous Sulfate-Induced Dopaminergic Cell Death in Cell Culture.
[So] Source:CNS Neurol Disord Drug Targets;15(10):1325-1332, 2016.
[Is] ISSN:1996-3181
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Dopamine agonists are utilized clinically as an initial treatment in younger Parkinson's disease patients to delay the side effects associated with commencement of levodopa medication. These agonists also serveas adjunctive therapeutics with levodopa to lower the incidence of adverse motor symptoms in advanced stages of the disease. OBJECTIVES: To compare the neuroprotective effects of the dopamine agonists pergolide and pramipexole on ferrous sulfate-induced neurotoxicity in dopaminergic neurons from primary mesencephalic cell culture. METHODS: Pergolide (0.001-1 µM) and pramipexole (0.01-200 µM) were administered to 8 day primary murine mesencephalic cultures for 24 h. in the presence or absence of desferal, sulpiride or cycloheximide. Ferrous sulfate (450 µM) was then added for 24 hrs. Lactate dehydrogenase was assayed in the supernatant, glutathione concentrations measured in cell lysates and fixed cells were stained for tyrosine hydroxylase. RESULTS: Ferrous sulphate induced neurotoxity in cultures (p<0.0001) was abolished in the presence of the iron chelator desferal (p<0.008). Both pergolide (p<0.0001) and pramipexole (p<0.0001) significantly protected dopaminergic neurons against ferrous sulfate induced neurotoxicity and pramipexole helped preserve neurite morphology. Pramipexole treatment significantly reduced lactate dehydrogenase release (p<0.0001) as a measure of cellular injury. The dopamine receptor antagonist sulpiride (p<0.0001) and the protein synthesis inhibitor cycloheximide (p<0.0001) reduced the neuroprotective effects of pergolide indicating the involvement receptor stimulation and de novo protein synthesis in pergolide-mediated neuroprotection. Pramipexole also significantly reversed the decrease in cellular glutathione concentrations induced by ferrous sulfate (p<0.001). CONCLUSION: Both pergolide and pramipexole protect dopaminergic neurons against the neurotoxicity of ferrous sulfate. Pergolide specifically protects dopaminergic neurons through activation of dopamine receptors and de novo protein synthesis whereas pramipexole shows an overall effect through an antioxidant mechanism.
[Mh] Termos MeSH primário: Benzotiazóis/farmacologia
Neurônios Dopaminérgicos/efeitos dos fármacos
Compostos Ferrosos/toxicidade
Fármacos Neuroprotetores/farmacologia
Pergolida/farmacologia
[Mh] Termos MeSH secundário: Animais
Morte Celular/efeitos dos fármacos
Cicloeximida/farmacologia
Relação Dose-Resposta a Droga
Interações Medicamentosas
Embrião de Mamíferos
Glutationa/metabolismo
L-Lactato Desidrogenase/metabolismo
Mesencéfalo/citologia
Camundongos
Camundongos Endogâmicos C57BL
Inibidores da Síntese de Proteínas/farmacologia
Estatísticas não Paramétricas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (Ferrous Compounds); 0 (Neuroprotective Agents); 0 (Protein Synthesis Inhibitors); 24MJ822NZ9 (Pergolide); 39R4TAN1VT (ferrous sulfate); 83619PEU5T (pramipexole); 98600C0908 (Cycloheximide); EC 1.1.1.27 (L-Lactate Dehydrogenase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160805
[St] Status:MEDLINE


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[PMID]:27174867
[Au] Autor:Capulli AK; MacQueen LA; O'Connor BB; Dauth S; Parker KK
[Ad] Endereço:Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA 02138, USA.
[Ti] Título:Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.
[So] Source:Cardiovasc Pathol;25(4):316-324, 2016 Jul-Aug.
[Is] ISSN:1879-1336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD.
[Mh] Termos MeSH primário: Valva Aórtica/efeitos dos fármacos
Agonistas de Dopamina/toxicidade
Técnicas In Vitro/métodos
Pergolida/toxicidade
Rigidez Vascular
[Mh] Termos MeSH secundário: Animais
Western Blotting
Avaliação Pré-Clínica de Medicamentos
Matriz Extracelular/efeitos dos fármacos
Matriz Extracelular/patologia
Fibroblastos/efeitos dos fármacos
Fibroblastos/patologia
Contração Muscular/efeitos dos fármacos
Suínos
Engenharia Tecidual/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Agonists); 24MJ822NZ9 (Pergolide)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160514
[St] Status:MEDLINE


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[PMID]:26415982
[Au] Autor:Uchida S; Soshiroda K; Okita E; Kawai-Uchida M; Mori A; Jenner P; Kanda T
[Ad] Endereço:Central Nervous System Research Laboratories, Central Nervous System Research & Development Unit, Research & Development Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
[Ti] Título:The adenosine A2A receptor antagonist, istradefylline enhances anti-parkinsonian activity induced by combined treatment with low doses of L-DOPA and dopamine agonists in MPTP-treated common marmosets.
[So] Source:Eur J Pharmacol;766:25-30, 2015 Nov 05.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The adenosine A2A receptor antagonist, istradefylline improves motor function in patients with advanced Parkinson's disease (PD) optimally treated with a combination of L-DOPA and a dopamine agonist without increasing the risk of troublesome dyskinesia. However, the effects of istradefylline on motor function when administered in combination with low dose of L-DOPA and dopamine agonists as occurs in early PD are unknown. We investigated whether istradefylline enhances the combined anti-parkinsonian effects of a suboptimal dose of L-DOPA and a threshold dose of either the non-ergot dopamine agonist, ropinirole or the ergot dopamine agonist, pergolide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. Threshold doses of ropinirole (0.025-0.075 mg/kg p.o.) and pergolide (0.01 mg/kg p.o.) produced a weak anti-parkinsonian effect. Co-administration of a suboptimal dose of L-DOPA (2.5mg/kg p.o.) with threshold doses of the dopamine agonists enhanced their anti-parkinsonian effect that led to increased 'ON' time without dyskinesia appearing. Administering istradefylline (10mg/kg p.o.) with the threshold doses of dopamine agonists and the suboptimal dose of L-DOPA in a triple combination caused a further enhancement of the anti-parkinsonian response but dyskinesia was still absent. In early PD, dopamine agonists are often used as first-line monotherapy, but efficacy is usually lost within a few years, at which time L-DOPA is added but with the risk of dyskinesia appearance. These results show that istradefylline is effective in improving motor function in combination with low dose dopaminergic drug treatment without provoking dyskinesia.
[Mh] Termos MeSH primário: Antagonistas do Receptor A2 de Adenosina/uso terapêutico
Antiparkinsonianos/uso terapêutico
Agonistas de Dopamina/uso terapêutico
Levodopa/uso terapêutico
Intoxicação por MPTP/tratamento farmacológico
Purinas/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Callithrix
Quimioterapia Combinada
Feminino
Indóis/uso terapêutico
Intoxicação por MPTP/induzido quimicamente
Masculino
Atividade Motora/efeitos dos fármacos
Pergolida/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenosine A2 Receptor Antagonists); 0 (Antiparkinson Agents); 0 (Dopamine Agonists); 0 (Indoles); 0 (Purines); 030PYR8953 (ropinirole); 24MJ822NZ9 (Pergolide); 2GZ0LIK7T4 (istradefylline); 46627O600J (Levodopa)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151027
[Lr] Data última revisão:
151027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150930
[St] Status:MEDLINE


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[PMID]:25629913
[Au] Autor:Rendle DI; Hughes KJ; Doran GS; Edwards SH
[Ad] Endereço:School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
[Ti] Título:Pharmacokinetics of pergolide after intravenous administration to horses.
[So] Source:Am J Vet Res;76(2):155-60, 2015 Feb.
[Is] ISSN:1943-5681
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To determine the pharmacokinetics of pergolide after IV administration to horses. ANIMALS: 8 healthy adult horses. PROCEDURES: Pergolide mesylate was administered IV at a dose of 20 µg/kg (equivalent to 15.2 µg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. RESULTS: After IV administration of pergolide, mean ± SD clearance, elimination half-life, and initial volume of distribution were 959 ± 492 mL/h/kg, 5.64 ± 2.36 hours, and 0.79 ± 0.32 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: With an elimination half-life of approximately 6 hours, twice-daily dosing may be more appropriate than once-daily dosing to reduce peak-trough fluctuation in pergolide concentrations. Further pharmacodynamic and pharmacokinetic studies of pergolide and its metabolites will be necessary to determine plasma concentrations that correlate with clinical effectiveness to determine the therapeutic range for the treatment of pituitary pars intermedia dysfunction.
[Mh] Termos MeSH primário: Agonistas de Dopamina/farmacocinética
Cavalos/metabolismo
Pergolida/farmacocinética
[Mh] Termos MeSH secundário: Administração Intravenosa
Animais
Cromatografia Líquida/veterinária
Agonistas de Dopamina/administração & dosagem
Agonistas de Dopamina/sangue
Masculino
Pergolida/administração & dosagem
Pergolida/sangue
Espectrometria de Massas em Tandem/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dopamine Agonists); 24MJ822NZ9 (Pergolide)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:150129
[Lr] Data última revisão:
150129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150129
[St] Status:MEDLINE
[do] DOI:10.2460/ajvr.76.2.155


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[PMID]:25499739
[Au] Autor:Uchida S; Soshiroda K; Okita E; Kawai-Uchida M; Mori A; Jenner P; Kanda T
[Ad] Endereço:Central Nervous System Research Laboratories, Central Nervous System Research & Development Unit, Research & Development Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8731, Japan.
[Ti] Título:The adenosine A2A receptor antagonist, istradefylline enhances the anti-parkinsonian activity of low doses of dopamine agonists in MPTP-treated common marmosets.
[So] Source:Eur J Pharmacol;747:160-5, 2015 Jan 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The adenosine A2A receptor antagonist, istradefylline, enhances anti-parkinsonian activity in patients with advanced Parkinson׳s disease (PD) already treated with combinations of L-DOPA and dopamine agonist drugs but who are still exhibiting prolonged 'OFF' periods. In contrast, the effects of istradefylline on motor function when administered in combination with low dose dopamine agonist therapy in early PD are unknown. We now investigate whether istradefylline administered with a threshold dose of either the non-ergot dopamine agonist, ropinirole or the ergot dopamine agonist, pergolide enhances anti-parkinsonian activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. Both ropinirole (0.01-0.1mg/kg p.o.) and pergolide (0.003-0.1mg/kg p.o.) administered alone produced dose dependent increases in locomotor activity, a reduction in motor disability. Threshold doses of ropinirole (0.025-0.075mg/kg p.o.) and pergolide (0.01-0.075mg/kg p.o.) were then selected that in individual animals caused a small but non-significant anti-parkinsonian effect. Administration of istradefylline (10mg/kg p.o.) alone resulted in a decrease in motor disability and increase in 'ON' time but dyskinesia was not observed. Combined administration of pergolide or ropinirole with istradefylline resulted in an increase in the reversal of motor disability and increase in 'ON' time compared to that produced by either treatment alone but dyskinesia was still not observed. These results show that istradefylline is effective in improving motor function when combined with low dose dopamine agonist treatment. In early PD, this may avoid dose escalation or allow a reduction in dopamine agonist dosage without a loss of efficacy and prevent dopaminergic side-effects from becoming treatment limiting.
[Mh] Termos MeSH primário: 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos
Antagonistas do Receptor A2 de Adenosina/farmacologia
Antiparkinsonianos/farmacologia
Agonistas de Dopamina/farmacologia
Purinas/farmacologia
Receptor A2A de Adenosina/metabolismo
[Mh] Termos MeSH secundário: Animais
Callithrix
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Feminino
Indóis/farmacologia
Levodopa/farmacologia
Masculino
Atividade Motora/efeitos dos fármacos
Pergolida/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenosine A2 Receptor Antagonists); 0 (Antiparkinson Agents); 0 (Dopamine Agonists); 0 (Indoles); 0 (Purines); 0 (Receptor, Adenosine A2A); 030PYR8953 (ropinirole); 24MJ822NZ9 (Pergolide); 2GZ0LIK7T4 (istradefylline); 46627O600J (Levodopa); 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:150126
[Lr] Data última revisão:
150126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141216
[St] Status:MEDLINE


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[PMID]:25312676
[Au] Autor:Rendle DI; Duz M; Beech J; Parkin T; Durham AE
[Ad] Endereço:The Liphook Equine Hospital, Liphook, Hampshire, UK.
[Ti] Título:Investigation of single and paired measurements of adrenocorticotropic hormone for the diagnosis of pituitary pars intermedia dysfunction in horses.
[So] Source:J Vet Intern Med;29(1):355-61, 2015 Jan.
[Is] ISSN:1939-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Paired measurement of ACTH concentration may be more reliable than a single measurement. HYPOTHESIS/OBJECTIVES: To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement. ANIMALS: Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars intermedia was performed in 67 of the untreated horses. METHODS: Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard. RESULTS: Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Paired measurement of ACTH concentration offers no advantage over a single measurement.
[Mh] Termos MeSH primário: Hormônio Adrenocorticotrópico/sangue
Doenças dos Cavalos/diagnóstico
Doenças da Hipófise/veterinária
Adeno-Hipófise Parte Intermédia/patologia
[Mh] Termos MeSH secundário: Animais
Agonistas de Dopamina/uso terapêutico
Feminino
Doenças dos Cavalos/sangue
Doenças dos Cavalos/tratamento farmacológico
Cavalos
Masculino
Pergolida/uso terapêutico
Doenças da Hipófise/sangue
Doenças da Hipófise/diagnóstico
Doenças da Hipófise/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Agonists); 24MJ822NZ9 (Pergolide); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141015
[St] Status:MEDLINE
[do] DOI:10.1111/jvim.12489


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[PMID]:25230720
[Au] Autor:Italiano D; Bianchini E; Ilardi M; Cilia R; Pezzoli G; Zanettini R; Vacca L; Stocchi F; Bramanti P; Ciurleo R; Di Lorenzo G; Polimeni G; de Luise C; Ross D; Rijnbeek P; Sturkenboom M; Trifirò G
[Ad] Endereço:Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
[Ti] Título:Effectiveness of risk minimization measures for cabergoline-induced cardiac valve fibrosis in clinical practice in Italy.
[So] Source:J Neural Transm (Vienna);122(6):799-808, 2015 Jun.
[Is] ISSN:1435-1463
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:On June 2008, the European Medicines Agency (EMA) introduced changes to the Summary of Product Characteristics (SPC) for cabergoline and pergolide, to reduce the risk of cardiac valvulopathy in users of these drugs. To assess the effectiveness of EMA recommendations in Italian clinical practice, we retrospectively reviewed medical charts of patients with degenerative Parkinsonism treated with cabergoline in three large Italian clinics between January 2006 and June 2012. The prevalence and the severity of cardiac valve regurgitation were assessed in patients who stopped cabergoline therapy prior to June 2008 or continued therapy after that date. In addition, the proportion of patients undergoing echocardiographic examination in each cohort was evaluated. A total of 61 patients were available for evaluation. The proportion of patients who underwent a baseline echocardiographic examination increased from 64 % in the period before the 2008 SPC changes to 71 % among those who continued treatment after that date. However, only 18 and 29 % of patients underwent at least two echocardiographic examinations during the pre-SPC and cross-SPC change period, respectively. No severe cardiac valve regurgitation was documented in any of the study patients using cabergoline either prior or after 26th June 2008. Our findings show that the 2008 changes to the SPC resulted in an increase in physicians' awareness of cabergoline-induced valvulopathy risk in Italy. However, only a small percentage of patients underwent serial echocardiography. Further efforts are needed to achieve better compliance with the prescribing guidelines for cabergoline treated patients in clinical practice.
[Mh] Termos MeSH primário: Antiparkinsonianos/uso terapêutico
Ergolinas/uso terapêutico
Doenças das Valvas Cardíacas/prevenção & controle
Pergolida/uso terapêutico
Guias de Prática Clínica como Assunto
[Mh] Termos MeSH secundário: Idoso
Antiparkinsonianos/efeitos adversos
Estudos de Coortes
Ecocardiografia
Ergolinas/efeitos adversos
Feminino
Fidelidade a Diretrizes
Doenças das Valvas Cardíacas/epidemiologia
Doenças das Valvas Cardíacas/fisiopatologia
Valvas Cardíacas/efeitos dos fármacos
Valvas Cardíacas/fisiopatologia
Seres Humanos
Incidência
Itália
Masculino
Meia-Idade
Doença de Parkinson/tratamento farmacológico
Doença de Parkinson/epidemiologia
Doença de Parkinson/fisiopatologia
Pergolida/efeitos adversos
Prevalência
Estudos Retrospectivos
Fatores de Risco
Paralisia Supranuclear Progressiva/tratamento farmacológico
Paralisia Supranuclear Progressiva/epidemiologia
Paralisia Supranuclear Progressiva/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Ergolines); 24MJ822NZ9 (Pergolide); LL60K9J05T (cabergoline)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140919
[St] Status:MEDLINE
[do] DOI:10.1007/s00702-014-1314-z



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