			Home About us Contact

Adrenoceptor-selective Antagonist (adrenoceptor-selective + antagonist)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Urodynamic effects of silodosin, a new ,1A -adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia,,

NEUROUROLOGY AND URODYNAMICS, Issue 4 2010
Tomonori Yamanishi
Abstract Aims To investigate urodynamically the effects of silodosin, a new ,1A -adrenoceptor-selective antagonist, in the treatment of benign prostatic hyperplasia (BPH). Methods Thirty six male patients with BPH (69.9,±,7.3 years), who were referred as candidates for surgery, were treated with silodosin (4,mg twice daily). The total International Prostate Symptom Score (IPSS) was 20.7,±,7.4, maximum flow rate (Qmax) was 6.7,±,3.0,ml/sec, and prostate volume was 45.6,±,24.5,ml. Results Total IPSS, storage and voiding symptom subscores and QOL score decreased significantly, and Qmax increased significantly after 1,12 months of therapy (all P,<,0.05). In urodynamic study (n,=,29), maximum cystometric capacity increased significantly (P,=,0.0027), and detrusor overactivity disappeared in 8 of 20 patients (40%) and improved (bladder capacity increased more than 50%) in 7 (35%) after the therapy. In pressure/flow studies (n,=,27), the obstruction grade was improved in 15 patients (56%). Detrusor opening pressure, detrusor pressure at Qmax, bladder outlet obstruction index, and Schäfer's obstruction class decreased significantly after therapy (all P,<,0.01). After 12 months, 16 patients (44%) are still on silodosin for 23.3,±,7.0 (range 12,36) months, and the improvements in IPSS and Qmax were stable. Twenty patients withdrew because of insufficient effectiveness in 13 patients (12 patients underwent surgery), side effects in 3, and unknown reasons in 4. Conclusion Silodosin appears to improve detrusor overactivity and obstruction grade in patients with BPH. With silodosin treatment, LUTS could be managed effectively for more than a year in at least 44% of the patients. Neurourol. Urodynam. 29:558,562, 2010. © 2009 Wiley-Liss, Inc. [source]

Alpha1A/L -adrenoceptors mediate contraction of the circular smooth muscle of the pig urethra

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2006
K. Bagot
Summary 1 Sympathetically mediated urethral tone is essential for the maintenance of continence and involves the activation of postjunctional ,1 -adrenoceptors. This study characterizes the ,1 -adrenoceptor subtypes responsible for mediating contraction of the urethral circular smooth muscle of the pig. 2 The potency order of a number of agonists and the affinities of several receptor selective antagonists were determined on pig-isolated circular smooth muscle strips in the presence of cocaine (1 ,m) and corticosterone (10 ,m) to inhibit amine uptake and propranolol (1 ,m) to antagonize , -adrenoceptors. 3 The potency order for agonists was N -[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulphonamide (A61603) > noradrenaline = phenylephrine = M6434 > methoxamine with pEC50 values of 7.3, 5.8, 5.7, 5.6 and 5.0 respectively. 4 The ,1D -adrenoceptor-selective antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione (BMY7378) caused rightward shifts of the concentration,response curves to noradrenaline, yielding a low affinity estimate (6.6) for the urethral receptor. The ,1A -adrenoceptor-selective antagonists, RS100329 and 5-methylurapidil, gave relatively high affinity estimates (9.6 and 8.8 respectively) for this receptor. All three antagonists produced Schild plots with slopes close to unity but did reduce maximum responses at higher concentrations. Prazosin antagonized responses of the urethra to noradrenaline, yielding a mean affinity estimate of 9.0. Although the Schild plot for prazosin again had a slope of unity, this drug also reduced maximum responses to noradrenaline at all concentrations examined (10,100 nm). N -[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro- ,,, -dimethyl-1H-indole-3-ethanamide (RS17053), which discriminates between responses mediated via ,1A (high affinity) and ,1L -adrenoceptors (low affinity) at concentrations up to 3 ,m, failed to antagonize responses of the urethra. 5 These results suggest that contraction of urethral circular smooth muscle in the pig is mediated via a single population of adrenoceptors with the pharmacological characteristics of the ,1A/L -adrenoceptor, most probably the ,1L -adrenoceptor. [source]

Activation Of ,1 -Adrenoceptors Is Not Essential For The Mediation Of Ischaemic Preconditioning In Rat Heart

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002
E Vasara
SUMMARY 1. The aim of the present study was to clarify the role of ,1 -adrenoceptors in the mechanism of ischaemic preconditioning (IP). 2. Rat isolated perfused hearts were either non- preconditioned, preconditioned with 5 min ischaemia or treated for 5 min with ,1 -adrenoceptor agonists (50 ,mol/L phenylephrine; 0.1, 0.5 and 1 ,mol/L methoxamine) before being subjected to 45 min of sustained ischaemia followed by 60 min reperfusion. 3. Within each of the above protocols, hearts were divided into groups to which ,1 -adrenoceptor antagonists (prazosin, 5,-methyl urapidil and chloroethylclonidine (CEC)) were administered. Functional recovery and infarct size were used as indices of the effects of ischaemia. Ischaemic contracture characteristics and maximal diastolic pressure during reflow were also assessed. 4. Blockade of ,1 -adrenoceptors with prazosin or the subtype-selective antagonists 5,-methyl urapidil and CEC did not abolish the protective effect of IP with respect to both functional recovery and infarct size reduction. 5. Protection afforded by phenylephrine was attenuated in hearts treated with prazosin or the ,1B -adrenoceptor- selective antagonist CEC, but not in those treated with the ,1A -adrenoceptor-selective antagonist 5,-methyl urapidil. 6. Treatment with low concentrations of methoxamine, considered to be ,1A -adrenoceptor selective, did not confer any protection to the ischaemic myocardium. 7. A close relationship between accelerated ischaemic contracture and enhanced cardioprotection was observed. 8. The results suggest that ,1 -adrenoceptor stimulation mimics IP, but it is not an essential component in the mechanism behind the protective effect of IP in rat heart. In addition, the present study demonstrates that stimulation of the ,1B - but not the ,1A -adrenoceptor subtype is responsible for the catecholamine-induced protection of ischaemic myocardium in rat. [source]