ABSTRACT
Overactive bladder (OAB) is a symptom-driven condition characterized by urinary urgency with or without urinary incontinence and a common problem that can significantly affect quality of life. Drugs that prevent acetylcholine-mediated involuntary detrusor contractions are the mainstay of OAB treatment, but several alternative therapeutic options have become established treatments for OAB. Mirabegron (a β3-adrenoceptor agonist) has a different mechanism of action from antimuscarinic agents. Recently published randomized controlled trials have shown that mirabegron is an effective and safe drug for the symptomatic treatment of OAB patients. Mirabegron represents a valid option both for patients with OAB who are antimuscarinics treatment-naïve, as well as for those who are unresponsive or intolerant to antimuscarinics. Intravesical injection of botulinum toxin A is an effective treatment for OAB that is refractory to antimuscarinics. Treatment with botulinum toxin A showed clinically relevant improvement in all OAB symptoms and health-related quality of life. It was generally well tolerated by most patients, and most treatment-related complications were acceptable. However, increased risk of a larger volume of post-void residual urine was noted in several patients and the possibility of chronic catheterization requires careful evaluation before treatment. In sum, recent options for management of OAB, mirabegron and intravesical injection of botulinum toxin A, expand the treatment options for the optimal treatment of each patient.
Subject(s)
Humans , Administration, Intravesical , Botulinum Toxins , Catheterization , Catheters , Drug Therapy , Muscarinic Antagonists , Quality of Life , Urinary Bladder, Overactive , Urinary IncontinenceABSTRACT
Objective To study the biological effect of ?3 adrenoceptor-activated electrophysiological activities in cardiac myocytes. Methods Changes of transient outward potassium ( Ito) and L-type calcium current ( ICa-L) in primary cultured guinea pig cardiacmyocytes were detected with the standard whole-cell patch clamp technique about 5 -10 min before and after administration of ?3 adrenoceptor agonist,4--2-hydroxy-( 3-chlorophenyl) ethyl-aminopropylphenoxyacetate ( BRL-37344; BRL). Results BRL could significantly increased the Ito in guinea pig cardiac myocytes with the I-V curve up-moved. When the membrane potential reached to + 80 mV,the density current increased from 6. 11 ? 1. 03 pA/pF to 8. 46 ? 2. 07 pA/pF ( n = 6,P =0. 013 064). BRL ( 10 -6mol/L) could significantly increase the ICa-Lin guinea pig cardiac myocytes,which was ( 2. 30 ?0. 75) -fold higher than in control group( n =5,P =0. 0063). When the membrane potential increased to + 10 mV ,the current,increased from 89. 25 ? 17. 83 pA to 205. 00 ? 72. 24 pA ( n = 5,P = 0. 006 3). Conclusion BRL-37344 can increase the transient Itoand ICa-L,thus further regulating the cardiac activities.
ABSTRACT
The human ?3-adrenoceptor plays an important role in the regulation of energy mobilization and utilization. A missense mutation in codon 64 of the gene for the ?3-adrenoceptor with a replacement of tryptophan to arginine (Trp64Arg) was found. This polymorphism influences receptor function when expressed in artificial cell lines or in isolated human fat cells. It is associated with an earlier onset of type 2 diabetes mellitus, features of insulin resistance and tendency to gain weight. Recent evidences suggest that Trp64Arg has additive and interactive effects with a number of other candidate gene variants. The functional significance of human ?3-adrenoceptor polymorphism and its association with metabolic diseases are reviewed in this paper.
ABSTRACT
Aim ?3 adrenoceptor(?3-AR) is predominantly expressed in white and brown adipose tissue.?3 adrenoceptor agonist stimulates the lipolysis of white adipose tissue and non-shivering thermogenesis of brown adipose tissue to exert its antiobese action.Moreover,?3 adrenoceptor agonist increases the sensitivity and response of adipose tissue to insulin and it play an important role in the treatment of type 2 diabetes.In addition,?3 adrenoceptor agonist can also relax gastrointestinal spasm and show cardiovascular effect in human heart and vascular tissues.There has been increasing concerned in the study and development of ?3 AR agonists since 1983.Up to date,32 kinds of ?3 AR agonists have been identified.The development of ?3 AR agonists can provide new strategy and approach for pharmacotherapy of obesity and diabetic mellitus and will have Spaciously the used out look in the field of medicine.