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Parkinsonism Relat Disord. 1997 Nov; 3(3): 171-2
Jost WH, Bellonx AK, Schimrigk K
Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD.
Neurology. 2008 Jun 25;
Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ,
BACKGROUND: Ten-year follow-up results from the PD Research Group of the United Kingdom trial demonstrated that there were no long-term advantages to initiating treatment with bromocriptine compared with L-dopa in early Parkinson disease (PD). Increased mortality in patients on selegiline combined with L-dopa led to premature termination of this arm after 6 years. METHODS: Between 1985 and 1990, 782 patients were recruited into an open pragmatic multicenter trial and were randomized to L-dopa/decarboxylase inhibitor (DDCI), L-dopa/DDCI plus selegiline, or bromocriptine. The main endpoints were mortality, disability, and motor complications. For final follow-up, health-related quality of life and mental function were also assessed. RESULTS: Median duration of follow-up at final assessment was 14 years in the 166 (21%) surviving participants who could be contacted. After adjustment for baseline characteristics, disability scores were better in the L-dopa than in the bromocriptine arm (Webster: 16.6 vs 19.8; p = 0.03; Northwestern University Disability: 34.3 vs 30.0, p = 0.05). Physical functioning (difference 20.8; 95% CI 10.0, 31.6; p < 0.001) and physical summary scores (difference 5.2; 95% CI 0.7, 9.7; p = 0.03) on the 36-item short-form health survey were also superior on L-dopa. Differences in mortality rates and prevalence of dyskinesias, motor fluctuations, and dementia were not significantly different. CONCLUSION: Initial treatment with the dopamine agonist bromocriptine did not reduce mortality or motor disability and the initially reduced frequency in motor complications was not sustained. We found no evidence of a long-term benefit or clinically relevant disease-modifying effect with initial dopamine agonist treatment.
J Endocrinol. 2008 Jul; 198(1): 209-17
Wang Z, Mitsui T, Ishida M, Arita J
Adenoviruses are powerful, widely utilized vectors for gene transfer. Limitations to their application, however, have not been well described. We used rat pituitary lactotrophs in primary culture as a model for studying how adenovirus vector infection modulates mitogen-induced proliferation and the activities of mitogen signaling pathways. Infection with adenovirus vectors expressing beta-galactosidase (betagal) raised basal proliferative levels and blocked fetal bovine serum (FBS)-induced proliferation of lactotrophs, but did not influence the changes in proliferation induced by forskolin, IGF-I, and bromocriptine. The betagal-expressing adenoviruses did not alter the inhibitory action of 17beta-estradiol (E(2)) in the presence of IGF-I; however, they blocked the stimulatory action of E(2) in the presence of dextran-coated charcoal-striped serum or forskolin. An adenovirus expressing no protein failed to block FBS-induced proliferation, but was effective in modulating basal proliferative levels and the stimulatory actions of E(2). The increased basal proliferative level and the blockade of FBS-induced proliferation were transient, and lost 5 days after infection while the blockade of the stimulatory action of E(2) in the presence of forskolin persisted. Adenovirus infection raised basal protein levels of the phosphorylated forms of cAMP response element-binding protein (pCREB) and ERK1/2 and increased the proportion of pCREB-immunoreactive lactotrophs. Adenoviruses also altered estrogen-induced responses in mRNA expression of several estrogen-responsive genes in a gene-specific manner. The results demonstrate that an adenovirus vector differentially interferes with lactotroph proliferation in response to various mitogens. Our results suggest that the effects of the adenovirus that are independent of the genes transferred must be considered when performing adenoviral gene transfer in the primary cultures of normal cells.
J Endocrinol Invest. 2008 May; 31(5): 436-44
Vilar L, Freitas MC, Naves LA, Casulari LA, Azevedo M, Montenegro R, Barros AI, Faria M, Nascimento GC, Lima JG, Nóbrega LH, Cruz TP, Mota A, Ramos A, Violante A, Lamounier Filho A, Gadelha MR, Czepielewski MA, Glezer A, Bronstein MD
OBJECTIVE: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyperprolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. DESIGN, SETTING, AND PATIENTS: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. MAIN OUTCOME MEASURE: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. RESULTS: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.
J Clin Endocrinol Metab. 2008 Jun 17;
Kok P, Roelfsema F, Frölich M, van Pelt J, Meinders AE, Pijl H
Context. A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2R). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signalling is mechanistically involved in the deficient GH secretion associated with obesity. Objective. To test this hypothesis we studied the effect of short-term bromocriptine (a D2R agonist) treatment on spontaneous 24 h GH secretion in obese women, while body weight and caloric intake remained constant. Design. Prospective, fixed order, cross-over study (2004). Setting. Clinical Research Center LUMC Participants. Eighteen healthy obese women (BMI 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle. Intervention(s). Eight days of treatment with bromocriptine (B) and placebo (Pl) Main Outcome Measure(s). Blood was collected during 24 hours at 10-minute intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis. Results. Short-term treatment with bromocriptine significantly enhanced diurnal GH secretion (Pl 121.4 +/- 16.4 vs. B 155.4 +/- 15.2 microg/Lvdl/24 hr, P = 0.01), whereas IGF-1 concentrations remained constant (Pl 22.4 +/- 2.4 vs. B 21.8 +/- 1.6 nmol/L, P = 0.928). Conclusion. Activation of dopamine D2 receptors by bromocriptine favourably affects impaired nyctohemeral GH secretion in obese women. Reduced dopaminergic neuronal signalling might be involved in the pathogenesis of obesity associated hyposomatotropism.
Brain Res. 2008 Jul 7; 1218: 54-69
Kessler M, Kiliman B, Humes C, Arai AC
Organotypic cerebellar cultures were maintained on multi-electrode dishes (MED) with an 8x8 array of electrodes and examined for physiological activity. The cultures remained viable for up to seven months and exhibited spontaneous discharges most likely originating from Purkinje cells. Spike frequencies varied but were mostly around 10-30 Hz and were often stable over weeks with average drifts of
Rotigotine: Parkinson's disease: a step backward.
Prescrire Int. 2008 Apr; 17(94): 60
In a clinical trial in patients with early-stage Parkinson's disease, rotigotine transdermal patches were less effective than oral ropinirole. In another trial, rotigotine was no more effective than pramipexole in patients with advanced Parkinson's disease. Transdermal delivery does not prevent the systemic adverse effects of rotigotine, and there is an additional risk of local reactions. Treatment is also more difficult to titrate. Patients with Parkinson's disease, whatever the stage, would be well advised to continue using an oral dopamine agonist such as bromocriptine.
Caution in the use of bromocriptine in peripartum cardiomyopathy.
J Am Coll Cardiol. 2008 May 27; 51(21): 2083; author reply 2083-4
Fett JD
Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.
J Endocrinol. 2008 May 19;
Bonomo I, Lisboa P, Passos M, Alves S, Reis A, Moura E
Malnutrition during lactation is associated with hypoprolactinaemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum T3. Maternal hypoprolactinaemia at the end of lactation caused higher body weight at adult life, suggesting an association of maternal prolactin (PRL) level and programming of the adult offspring's body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD), liver and pituitary deiodinases activities (D1 and/or D2) and 'in vitro' post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into: BRO- injected with 1mg/twice a day, daily for the last 3 days of lactation and C- control, saline-injected with the same frequency. At 180 days old, the offspring were injected with 125I ip and after 2h, they were sacrificed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (-51%), T3 (-23%) and T4 (-21%), lower thyroid 125I uptake (-41%), liver mGPD (-55%) and pituitary D2 (-51%) activities, without changes in the 'in vitro' post-TRH TSH release. We evidenced that maternal PRL supression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.
J Clin Psychopharmacol. 2008 Jun; 28(3): 264-370
Yuan HN, Wang CY, Sze CW, Tong Y, Tan QR, Feng XJ, Liu RM, Zhang JZ, Zhang YB, Zhang ZJ
Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.