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Mechanism and treatment of dropped head syndrome associated with parkinsonism.
Parkinsonism Relat Disord. 2008 Jun 21;
Oyama G, Hayashi A, Mizuno Y, Hattori N
Dropped head syndrome (DHS) associated with parkinsonism is not frequent, but it markedly reduces the activities of daily living and is refractory. To elucidate the mechanism and treatment of DHS associated with parkinsonism, we assessed 28 parkinsonian patients with DHS (2 men and 26 women) by examining their clinical features and cervical-muscle-needle and surface electromyographic (EMG) recordings. We also evaluated the effects of lidocaine, muscle afferent block (MAB; 1% lidocaine mixed with ethanol), and botulinum toxin injected into the bilateral sternocleidomastoid muscles (SCMs), which were considered to be the affected muscles. In some patients, DHS occurred after the initiation or loading of dopamine agonists (less common after pergolide than cabergoline and pramipexole). Improvement was noted after a reduction in the dopamine agonist dose in some patients, and loading of l-dopa in others. Needle EMG revealed no evidence for weakness of the dorsal neck muscles. Surface EMG showed a gradual increase in SCMs activity upon passive head lifting. Lidocaine injection into SCMs markedly improved DHS, but the effect was temporary. The effect of botulinum toxin and MAB was not satisfactory. Whereas DHS could have a heterogeneous etiology, dopamine receptor sensitivity may play a role in its pathogenesis. For the treatment of DHS in parkinsonian patients, an increase in the dosage of l-dopa and a decrease in that of the dopamine agonist should be considered. Lidocaine injection (lidocaine test) could be useful for determining the most affected muscle before using botulinum toxin or MAB. Further studies are needed to examine the outcome of such treatments that include GPi-DBS.
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;
Kars M, Delgado V, Holman ER, Feelders RA, Smit JW, Romijn JA, Bax JJ, Pereira AM
Objective: Treatment with ergot-derived dopamine agonists, pergolide and cabergoline, has been associated with an increased frequency of valvular heart disease in Parkinson's disease. The aim of the present study was to assess the prevalence of valvular heart disease in patients treated with dopamine agonists for prolactinomas. Design: Cross-sectional study Patients: We performed two-dimensional and Doppler echocardiography in 78 consecutive patients with prolactinoma (mean age 47 +/- 1.4 yr, 26% male, 31% macroprolactinoma) treated with dopamine agonists for at least 1 year (mean 8 +/- 0.6 yr) and 78 control subjects. Patients were classified according to treatment: patients treated with cabergoline (group 1: n=47), and patients not treated with cabergoline (group 2: n=31). Results: Clinically relevant valvular heart disease was present in 12% (9 of 78) of patients vs. 17% (13 of 78) of controls (P=0.141), and in 17% (8 of 47) of patients treated with cabergoline vs. 3% (1 of 31) of patients not treated with cabergoline (P=0.062). Mild tricuspid regurgitation was present in 41% of patients vs. 26% of controls (P=0.042), and aortic valve calcification was present in 40% of patients compared to 18% of controls (P=0.003). There was no relation between the cumulative dose of cabergoline and the presence of mild, moderate or severe valve regurgitation. Conclusion: Several years of dopamine agonist treatment in patients with prolactinomas is associated with increased prevalence of aortic valve calcification and mild tricuspid regurgitation, but not with clinically relevant valvular heart disease. Therefore, additional studies on the adverse cardiac effects of dopaminergic drugs in prolactinoma are warranted, especially in patients with much longer use of these drugs.
Endocr Relat Cancer. 2008 Jun; 15(2): 583-596
Florio T, Barbieri F, Spaziante R, Zona G, Hofland LJ, van Koetsveld PM, Feelders RA, Stalla GK, Theodoropoulou M, Culler MD, Dong J, Taylor JE, Moreau JP, Saveanu A, Gunz G, Dufour H, Jaquet P
Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [(3)H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC(50)=1.2 pM and E(max)=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs.
J Neurol. 2008 Jun 2;
Placidi F, Izzi F, Romigi A, Stanzione P, Marciani MG, Brusa L, Sperli F, Galati S, Pasqualetti P, Pierantozzi M
OBJECTIVE : To investigate the sleep-wake cycle and the effects of cabergoline monotherapy in a homogenous group of de novo Parkinson's Disease (PD) patients without confounding comorbid factors. DESIGN AND PARTICIPANTS : Twelve de novo patients affected by idiopathic PD underwent two ambulatory polysomnographic (APSG) monitoring sessions. The first was performed at baseline, and the second recording one-month after stable treatment with cabergoline monotherapy. Subjective daytime sleepiness was evaluated by means of the Epworth Sleepiness Scale. Data obtained in PD patients at baseline were compared with those obtained in 12 age- and sexmatched healthy subjects. RESULTS : Diurnal sleep parameters did not show significant differences between controls and PD patients at baseline. In PD patients, no significant changes in diurnal sleep were observed between baseline and cabergoline treatment. Regarding nocturnal sleep, patients at baseline showed a significantly lower sleep efficiency and a significantly higher Wakefulness After Sleep Onset than controls. With respect to baseline, a significant increase in REM latency and a significant reduction in REM sleep were observed during cabergoline treatment. CONCLUSIONS : In the early stage of PD, the neurodegenerative process does not seem to be directly responsible for daytime somnolence, but it may be directly involved in the alteration of nocturnal sleep. Cabergoline monotherapy does not affect daytime sleep propensity and, despite clinical improvement, it may have negative effects on REM sleep.
Remission in Cushing disease with cabergoline.
Ann Saudi Med. 2008 May-Jun; 28(3): 224-5
Gopal R, Bandgar T, Menon P, Shah N
TSH-secreting adenoma improved with cabergoline.
Ann Endocrinol (Paris). 2008 Jun; 69(3): 244-248
Mouton F, Faivre-Defrance F, Cortet-Rudelli C, Assaker R, Soto-Ares G, Defoort-Dhellemmes S, Blond S, Wemeau JL, Vantyghem MC
TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.
[Sexual dysfunctions induced by antidepressants and antipsychotics]
Rev Med Suisse. 2008 Mar 26; 4(150): 758-62
Martin-Du PR, Baumann P
Depressive and schizophrenic patients frequently suffer from sexual dysfunctions. Antidepressants and antipsychotics can aggravate them leading to discontinuation of the treatment. The strategy to decrease these dysfunctions is the following: 1) reducing the dose of medication; 2) changing antidepressant: replace SSRI by moclobemid, trazodone, bupropion, mirtazpine, which do not delay ejaculation; switching to another antipsychotic: quietiapine, olanzapine, aripripazol, which do not increase serum prolactin; 3) taking a drug holiday for two or three days and 4) adding another drug such as sildenafil if impotence, or a dopaminergic agonist (aripripazol, a partial agonist) or cabergoline, in case of hyperprolactinaemia.
Int J Clin Pract. 2008 May 6;
Bogazzi F, Buralli S, Manetti L, Raffaelli V, Cigni T, Lombardi M, Boresi F, Taddei S, Salvetti A, Martino E
Introduction and aim: Dopamine agonists have been reported to increase the risk of cardiac valve regurgitation in patients with Parkinson's disease. However, it is unknown whether these drugs might be harmful for patients with hyperprolactinaemia (HyperPRL). The aim of the study was to evaluate whether HyperPRL patients treated with dopamine agonists had a higher prevalence of cardiac valves regurgitation than that of general population. Methods and patients: One hundred consecutive patients (79 women, 21 men, mean age 41 +/- 13 years) with HyperPRL during treatment with cabergoline were enrolled in an observational case-control study and compared with 100 matched normal subjects (controls). Valve regurgitation was assessed by echocardiography according to the American Society of Echocardiography recommendations. Results: Seven HyperPRL patients (7%) and six controls (6%) had moderate (grade 3) regurgitation in any valve (p = 0.980). All were asymptomatic and had no signs of cardiac disease. Mean duration of cabergoline treatment was 67 +/- 39 months (range: 3-199 months). Mean cumulative dose of cabergoline was 279 +/- 301 mg (range: 15-1327 mg). Moderate valve regurgitation was not associated with the duration of treatment (p = 0.359), with cumulative dose of cabergoline (p = 0.173), with age (p = 0.281), with previous treatment with bromocriptine (p = 0.673) or previous adenomectomy (p = 0.497) in patients with HyperPRL. Discussion: In conclusion, treatment with cabergoline was not associated with increased prevalence of cardiac valves regurgitation in patients with HyperPRL. Mean cumulative dose of cabergoline was lower in patients with HyperPRL than that reported to be deleterious for patients with Parkinson's disease: hence, longer follow-up is necessary, particularly in patients receiving weekly doses > 3 mg.
Cabergoline and the risk of valvular lesions in endocrine disease.
Eur J Endocrinol. 2008 Jul; 159(1): 1-5
Lancellotti P, Livadariu E, Markov M, Daly AF, Burlacu MC, Betea D, Pierard L, Beckers A
AIMS: The cardiac valvular risk associated with lower exposure to cabergoline in common endocrine conditions such as hyperprolactinemia is unknown. METHODS AND RESULTS: We performed a cross-sectional, case-control echocardiographic study to assess the valvular status in 102 subjects receiving cabergoline for endocrine disorders and 51 matched control subjects. Cabergoline treatment ranged from 12 to 228 months, with a cumulative dose of 18-1718 mg. Valvular regurgitation was equally prevalent in both groups and was almost exclusively mild. Two cabergoline-treated subjects had moderate mitral regurgitation; there was no relationship between cabergoline dose and the presence or severity of mitral valve regurgitation (P=NS). Mitral valve tenting area was significantly greater in the cabergoline group when compared with the control subjects (P=0.03). Mitral valve leaflet thickening was observed in 5.9% of cabergoline-treated subjects; no relationship with the cumulative cabergoline dose was found. No patient had aortic or tricuspid valvular restriction. CONCLUSION: No significantly increased risk of clinically relevant cardiac valve disorders was found in subjects treated with long-term cabergoline therapy at the doses used in endocrine practice. While exposure to cabergoline appears to be safe during low-dose long-term therapy, an association with subclinical changes in mitral valve geometry cannot be completely excluded.