Effects of norepinephrine on rat cultured microglial cells that express α1, α2, β1 and β2 adrenergic receptors

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVE
To assess the effect on sexual function of alfuzosin 10 mg once daily, a uroselective α1-blocker, in men with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction.

PATIENTS AND METHODS
In all, 3076 men (mean age 65.9 years) were treated for 1 year with alfuzosin 10 mg in ‘real life’ practice. They were asked to complete the International Prostatic Symptom Score (IPSS), its appended eighth question (bother score) and the Danish Prostatic Symptom Score questionnaire for sexual dysfunction (DAN-PSSsex). The results were analysed at the endpoint in the intent-to-treat population.

RESULTS
At baseline, 2434 (79.1%) men were sexually active and answered correctly at least one item of the DAN-PSSsex. Sexual dysfunction was highly prevalent (reduced stiffness of erection, 65.3%; reduced volume of ejaculate, 63.2%; pain/discomfort on ejaculation, 20.2%), and was strongly related to the severity of LUTS and impairment of quality of life. At the endpoint, alfuzosin significantly improved the total IPSS (−6.1, − 32%) and bother score (−1.4, − 33.2%, both P < 0.001) over baseline. In those men with sexual dysfunction there were significant improvements in weighted scores related to reduced rigidity of erection (−0.5), reduced amount of ejaculate (−0.4) and pain/discomfort on ejaculation (−1.2, all P < 0.001) over baseline. The perceived improvements were more marked in men with severe LUTS or a severe bother score at baseline.

CONCLUSIONS
Sexual dysfunction is highly prevalent in men with LUTS and related to the baseline IPSS and bother score. Alfuzosin 10 mg once daily for 1 year is effective in improving LUTS and quality of life, and is well tolerated. It may even improve sexual function in those men with concomitant erectile and/or ejaculatory dysfunction.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2005.05347.x

Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction.

OBJECTIVE

To assess the effects of the α1-adrenoceptor antagonists alfuzosin and tamsulosin on the physiological events associated with ejaculation in the rat, because when these drugs are used for treating symptomatic benign prostatic hyperplasia in men they may affect ejaculation by impairing bladder neck closure and seminal vesicle contraction.



MATERIALS AND METHODS

In clinical trials the incidence of ejaculatory disorders in men is typically < 1% with alfuzosin and 4–18% with tamsulosin. The effects of tamsulosin and alfuzosin on bladder neck and seminal vesicle pressures (BNP and SVP) in the rat were analysed. Increases in BNP and SVP were induced in urethane-anaesthetized Wistar rats by electrical stimulation (ES) of the hypogastric nerve (HN) before and after an intravenous injection with vehicle, 3 or 10 µg/kg of tamsulosin or alfuzosin (10 rats/group). The mean amplitude and area under the curve (AUC) of the BNP and SVP were expressed as the percentage of the response to ES of HN before the treatment.



RESULTS

The amplitude and AUC of the SVP were significantly decreased by both doses of tamsulosin, and marginally decreased by the same doses of alfuzosin. The amplitude of the BNP was significantly decreased by 3 and 10 µg/kg of tamsulosin and 10 µg/kg alfuzosin, and marginally decreased by 3 µg/kg alfuzosin. The AUC of the BNP was significantly decreased by both doses of tamsulosin, but barely affected by alfuzosin at the same doses.



CONCLUSION

Over the doses assessed, alfuzosin had significantly less deleterious effect on increases in BNP and SVP induced by ES of the HN than had tamsulosin.

A comparison of the effects of tamsulosin and alfuzosin on neurally evoked increases in bladder neck and seminal vesicle pressure in rats.

Ejaculation disorders are associated with tamsulosin treatment for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). To assess whether tamsulosin has any effect on semen, sperm parameters were evaluated in healthy men receiving tamsulosin, alfuzosin, and placebo. Forty-eight healthy men received 5 days of tamsulosin 0.8 mg once daily (QD), alfuzosin 10 mg QD, and placebo in a randomized, double-blind, 3-way crossover study with a 10-14-day washout period between treatments. The changes (x +/- SE) from baseline in semen sperm concentration, semen sperm count, semen viscosity, semen fructose, sperm motility, and sperm morphology on day 5 of treatment were assessed. The change from baseline in semen sperm concentration was 3.1 +/- 8.3 million/mL with tamsulosin, 15.0 +/- 6.5 million/mL with alfuzosin, and 24.4 +/- 6.5 million/mL with placebo. The total sperm count in semen decreased from baseline with tamsulosin (-54.6 +/- 24.0 million) but not with placebo (81.5 +/- 18.8 million) or alfuzosin (46.2 +/- 19.0 million). The percentage of men with normal semen viscosity was lower with tamsulosin (65%) than with placebo (98%) or alfuzosin (92%). The change from baseline in semen fructose was comparable for all treatments. The percentage of motile sperm decreased 13.8% from baseline to day 5 of treatment with tamsulosin compared with decreases of 2.3% with placebo and 0.4% with alfuzosin. The percentage of abnormal sperm increased marginally with tamsulosin (0.6%) but not with placebo (-2.8%) or alfuzosin (-3.9%). The most common adverse events were dizziness (alfuzosin 11%, tamsulosin 14%, placebo 0%) and orthostatic hypotension (alfuzosin 25%, tamsulosin 11%, placebo 5%). The results suggest that tamsulosin has a negative effect on sperm in healthy men. Studies on the effects of alpha(1)-adrenergic blockers on sperm in men with BPH are warranted.

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.108.006874

Effects of Alfuzosin and Tamsulosin on Sperm Parameters in Healthy Men: Results of a Short‐Term, Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study

α1 -Adrenoceptors are seven transmembrane domain GPCRs involved in numerous physiological functions controlled by the endogenous catecholamines, noradrenaline and adrenaline, and targeted by drugs useful in therapeutics. Three separate genes, whose products are named α1A -, α1B -, and α1D - adrenoceptors, encode these receptors. Although the existence of multiple α1 -adrenoceptors has been acknowledged for almost 25 years, the specific functions regulated by each subtype are still largely unknown. Despite the limited comprehension, the identification of a single class of subtype-selective ligands for the α1A - adrenoceptors, the so-called α-blockers for prostate dysfunction, has led to major improvement in therapeutics, demonstrating the need for continued efforts in the field. This review article surveys the tissue distribution of the three α1 -adrenoceptor subtypes in the cardiovascular system, genitourinary system, and CNS, highlighting the functions already identified as mediated by the predominant activation of specific subtypes. In addition, this review covers the recent advances in the understanding of the molecular mechanisms involved in the regulation of each of the α1 -adrenoceptor subtypes by phosphorylation and interaction with proteins involved in their desensitization and internalization. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14617

Updates in the function and regulation of α1 -adrenoceptors.

Expression and pharmacological characterization of α1-adrenoceptors in rat seminal vesicle

Sweeteners are frequently used by women of reproductive age. This is a narrative review about the sweeteners currently sold in the Brazilian commerce. There is a few information on the use of saccharin and cyclamates in pregnancy and their effects on the fetus. Due to the limited information available and their carcinogenic potential in animal species, saccharin and cyclamates should be avoided during pregnancy (risk C). Aspartame has been extensively studied in animals and it is considered safe for use during pregnancy (risk B), except by women homozygous for phenylketonuria (risk C). Sucralose and acessulfame-K are not toxic, carcinogenic or mutagenic in animals, but there are no controlled studies in humans. However, since these two sweeteners are not metabolized, it is unlikely that their use during pregnancy could be harmful (risk B). Stevia, a substance extracted from a native Brazilian plant, is innocuous in animal pregnancies, but there are no controlled studies in humans (risk B). Body agents found in the composition of artificial sweeteners (mannitol, sorbitol, xylitol, erithrol, lactilol, isomalt, maltilol, lactose, fructose, maltodextrin, dextrin, and inverted sugar) are substances generally regarded as safe for human consumption. In conclusion, according to the currently available evidence, aspartame, sucralose, acessulfame-K and stevia can be safely used during pregnancy.

/pdf/o-uso-de-adocantes-na-gravidez-uma-analise-dos-produtos-46rfuwbkl3.pdf

Alexandre Megale

Papers

Expression and pharmacological characterization of α1-adrenoceptors in rat seminal vesicle

O uso de adoçantes na gravidez: uma análise dos produtos disponíveis no Brasil