Exposure to Glycolysis-Enhancing Drugs and Risk of Parkinson's Disease: A Meta-Analysis.

Background: Impaired glucose and energy metabolism has been suggested as a pathogenic mechanism underlying Parkinson's disease (PD). In recent cohorts, phosphoglycerate kinase 1 activators (PGK1a) have been associated with a lower incidence of PD when compared with other antiprostatic agents that do not activate PGK1. Objective: We aimed to perform a systematic review and meta-analysis comparing the incidence of PD in patients taking PGK1a versus tamsulosin. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PGK1a vs. tamsulosin in adults and elderly. The primary outcome was the incidence of PD. We computed hazard ratios (HR) for binary endpoints, with 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager 5.4 and R (version 4.3.1). Results: A total of 678,433 participants from four cohort studies were included, of whom 287,080 (42.3%) received PGK1a. Mean age ranged from 62 to 74.7 years and nearly all patients were male. Patients taking PGK1a had a lower incidence of PD (PGK1a 1.04% vs. tamsulosin 1.31%; HR 0.80; 95% CI 0.71-0.90; p < 0.01). This result remained consistent in a sensitivity analysis excluding patients of age 60 years old or younger (PGK1a 1.21% vs. tamsulosin 1.42%; HR 0.82; 95% CI 0.71-0.95; p < 0.01). Conclusions: Glycolysis-enhancing drugs are associated with a lower incidence of PD when compared with tamsulosin in adults and elderly individuals with prostatic disease in use of alpha-blockers. Our findings support the notion of glycolysis as a potential neuroprotective mechanism in PD. Future investigations with randomized controlled trials are needed.

It has been suggested that impairment in glucose and energy metabolism is one of the mechanisms underlying the development of Parkinson's disease. In recent studies, medications traditionally prescribed for prostate diseases, called phosphoglycerate kinase 1 activators (PGK1a), have been associated with a lower incidence of Parkinson's disease when compared to other medications for the same purpose that do not activate the same energetic pathway. Therefore, we thoroughly reviewed the literature and combined the results of studies that compared both medications (PGK1a versus another medication  that  does not activate this energetic pathway, called tamsulosin), evaluating the incidence of Parkinson's disease in both groups. We included a total of 678,433 individuals, of whom 42.3% received PGK1a and 57.7% received tamsulosin. In our analysis, patients taking PGK1a had a lower incidence of Parkinson's disease when compared to the other group, even when we excluded patients younger than 60 years of age. As a result, our findings support the notion that the increase of energy metabolism is a potential neuroprotective mechanism in Parkinson's disease and future investigations are needed.

Tamsulosin facilitates depressive-like behaviors in mice: Involvement of endogenous glucocorticoids.

The benign prostatic hyperplasia (BPH) is the main source of lower urinary tract symptoms. The BPH is a common age-dependent disease and tamsulosin is an α1-adrenoceptor blocker widely prescribed for BPH. Beyond the common adverse effects of tamsulosin, increased diagnosis of dementia after prescription was observed. Importantly, a clinical study suggested that tamsulosin may exert antidepressant effects in BPH patients. Considering the expression of α1-adrenoceptors in the brain, this study aimed to investigate the effects of tamsulosin in the forced swimming and open field tests in mice. For this, tamsulosin (0.001-1 mg/kg) was orally administered subacutely (1, 5 and 23 hr) and acutely (60 min) before tests. Mifepristone (10 mg/kg), a glucocorticoid receptor antagonist, and aminoglutethimide (10 mg/kg), a streoidogenesis inhibitor, were intraperitoneally injected before tamsulosin to investigate the role of the hypothalamic-pituitary-adrenal axis in the mediation of tamsulosin-induced effects. Subacute and acute administrations of tamsulosin increased the immobility time in the first exposition to an inescapable stressful situation. In the re-exposition to the swim task, controls displayed a natural increase in the immobility time, and the treatment with tamsulosin further increased this behavioral parameter. Tamsuslosin did not affect spontaneous locomotion neither in naïve nor in stressed mice. Our findings also showed that mifepristone and aminoglutethimide prevented the tamsulosin-induced increase in the immobility time in the first and second swimming sessions, respectively. In conclusion, tamsulosin may contribute to increased susceptibility to depressive-like behaviors, by facilitating the acquisition of a passive stress-copying strategy. These effects seem to be dependent on endogenous glucocorticoids.

Effectiveness of medical expulsive therapy with the ɲ-adrenergic blocker tamsulosin for distal ureterolithiasis in adults attended in an emergency department in Chile. / Efectividad del tratamiento médico expulsivo con el bloqueador alfa tamsulosina en pacientes adultos que consultan por cálculo ureteral distal en un servicio de urgencias chileno.

OBJECTIVES: To assess the effectiveness of medical expulsive therapy with tamsulosin. MATERIAL AND METHODS: Randomized double-blind controlled trial in an emergency department. We enrolled adults with uncomplicated distal ureterolithiasis and no other complaint. Patients were randomized to take either tamsulosin (0.4 mg/d) plus a nonsteroidal anti-inflammatory drug (NSAID) or placebo plus the NSAID for 21 days. RESULTS: The stone expulsion rate did not differ statistically between the 2 groups (P=.29). Time until expulsion was also similar (P=.91). CONCLUSION: Medical expulsive therapy with tamsulosin does not improve the rate of distal ureteral stone expulsion.

OBJETIVO: Evaluar la efectividad del tratamiento médico expulsivo con tamsulosina. METODO: Ensayo clínico prospectivo aleatorizado doble ciego realizado en un servicio de urgencias. Se incluyen adultos con ureterolitiasis distal única no complicada, que fueron asignados aleatoriamente a tamsulosina 0,4 mg/día más antiinflamatorio no esteroideo (AINE) (grupo A), o con placebo más AINE (grupo B), durante 21 días. RESULTADOS: No se observaron diferencias estadísticamente significativas en la tasa de expulsión de litiasis entre ambos grupos (p = 0,29) ni en el tiempo de expulsión de esta (p = 0,91). CONCLUSIONES: La terapia expulsiva con tamsulosina no se asocia a una mayor tasa de expulsión de litiasis ureteral.

Atividade antiandrogênica no tratamento da hiperplasia prostática benigna com nanocarreadores transdérmicos de dose combinada (tansulosina e dutasterida) / Antiandrogenic activity in Benign Prostatic Hyperplasia treatment with combined nanocarriers transdermal dose (tamsulosin and dutasteride)

Benign prostatic hyperplasia (BPH) is one of the most common diseases of the urogenital tract. Thisstudy aimed to obtain one transdermal microemulsion of dutasteride and tamsulosin, drugs used in the treatmentof BPH, characterize them and study your in vitro release, evaluating through in vivo studies the antiandrogenicactivity of transdermal microemulsion. The preparation of the formulation involved obtaining the microemulsionwith Dutasteride and Tamsulosin in the equivalent percentage of 0.2% for each drug. To carry out theantiandrogenic activity, were used 32 rats (Wistar) in four groups experimental. The characterization performedall formulations showed good results, in which the evaluation of anti-hyperplastic the microemulsiondemonstrated one reducing the organs testosterone-dependent (prostate and seminal vesicles) corroborated forthe study in question enabling then obtaining promising transdermal formulations for BPH treatment, presentingthus a therapeutic alternative to conventional treatments.

Atividade antiandrogênica no tratamento da hiperplasia prostática benigna com nanocarreadores transdérmicos de dose combinada (tansulosina e dutasterida) / Antiandrogenic activity in Benign Prostatic Hyperplasia treatment with combined nanocarriers transdermal dose (tamsulosin and dutasteride)

Benign prostatic hyperplasia (BPH) is one of the most common diseases of the urogenital tract. Thisstudy aimed to obtain one transdermal microemulsion of dutasteride and tamsulosin, drugs used in the treatmentof BPH, characterize them and study your in vitro release, evaluating through in vivo studies the antiandrogenicactivity of transdermal microemulsion. The preparation of the formulation involved obtaining the microemulsionwith Dutasteride and Tamsulosin in the equivalent percentage of 0.2% for each drug. To carry out theantiandrogenic activity, were used 32 rats (Wistar) in four groups experimental. The characterization performedall formulations showed good results, in which the evaluation of anti-hyperplastic the microemulsiondemonstrated one reducing the organs testosterone-dependent (prostate and seminal vesicles) corroborated forthe study in question enabling then obtaining promising transdermal formulations for BPH treatment, presentingthus a therapeutic alternative to conventional treatments.(AU)