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Adrenergic Antagonist (adrenergic + antagonist)

Distribution by Scientific Domains

Medical Sciences	90%

Selected Abstracts

A Pilot Trial of the Alpha-1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence

ALCOHOLISM, Issue 2 2009
Tracy L. Simpson
Background:, Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the ,-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD. Methods:, We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number. Results:, Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions. Conclusions:, Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial. [source]

Structure,activity relationships of isoeugenol-based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidation

DRUG DEVELOPMENT RESEARCH, Issue 5 2010
Kuo-Ping Shen
Abstract Three isoeugenol-based eugenosedin chlorphenylpiperazine derivatives, Eu-A, Eu-B, and Eu-C, were synthesized and tested for their serotonergic, adrenergic antagonist, antioxidant, and anti-aggregation activities. In radioligand binding assays, all three agents displayed significant binding affinities on ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptors. In human platelet, they inhibited epinephrine and 5-HT-induced aggregation, and in human platelet with ,2 and 5-HT2A receptors they had a competitive binding effect. Eu-B and Eu-C were more potent than Eu-A. All compounds had antioxidant effects derived from aryloxypropanolamine. Eu- A, Eu-B, or Eu-C (1, 3, 5,mg/kg iv) given to normotensive Wistar rats produced a dose-dependent decrease in mean arterial blood pressure and heart rate and when injected into the cisternum, Eu-A, Eu-B, or Eu-C (0.3, 0.03,µmol) increased blood pressure within 15,min. Pretreatment with any of the three agents inhibited clonidine (38,pmol)-induced hypotension. In vitro experiments, Eu-A, Eu-B, or Eu-C (1, 10, and 100,µM) competitively antagonized norepinephrine-, clonidine-, and 5-HT (10,8,10,4,M)-induced vasocontraction in isolated rat aorta, and competitively antagonized isoproterenol (10,8,10,4,M)-induced positive inotropic effects in a concentration-dependent manner in the isolated rat left atrium. In isolated rabbit ear arteries sensitized with 16,mM K+, all three agents antagonized 5-nonyloxytryptamine- and 5-HT-induced vasocontractions. These findings show that Eu-A, Eu-B, and Eu-C possess functional ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptor blocking activities. In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor antagonistic activities, but not anti-aggregation and antioxidant activities. Drug Dev Res 71:1,9, 2010. © 2010 Wiley-Liss, Inc. [source]

The pharmacological properties of anisodamine,

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2007
Jay M. Poupko
Abstract Anisodamine is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in the People's Republic of China. Like atropine and scopolamine, anisodamine is a non-specific cholinergic antagonist exhibiting the usual spectrum of pharmacological effects of this drug class. It appears to be less potent and less toxic than atropine and displays less CNS toxicity than scopolamine. Anisodamine has been shown to interact with and disrupt liposome structure which may reflect its effects on cellular membranes. Experimental evidence implicates anisodamine as an anti-oxidant that may protect against free radical-induced cellular damage. Its cardiovascular properties include depression of cardiac conduction and the ability to protect against arrhythmia induced by various agents. Anisodamine is a relatively weak ,1 adrenergic antagonist which may explain its vasodilating activity. Its anti-thrombotic activity may be a result of inhibition of thromboxane synthesis. The T1/2 of anisodamine in humans is about 2,3 h. Numerous therapeutic uses of anisodamine have been proposed including treatment of septic shock, various circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers, gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake bite and radiation damage protection. The primary therapeutic use of anisodamine has been for the treatment of septic shock. Several mechanisms have been proposed to explain its beneficial effect though most mechanisms are based upon the assumption that anisodamine ultimately acts by an improvement of blood flow in the microcirculation. Preliminary studies suggest another important therapeutic use of anisodamine is for the treatment of OP poisoning. Additional research is needed to delineate further the clinical usefulness of anisodamine relative to other anti-muscarinic drugs such as atropine and scopolamine. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Neural Circuits Regulating Pulsatile Luteinizing Hormone Release in the Female Guinea-Pig: Opioid, Adrenergic and Serotonergic Interactions

JOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2001
A. C. Gore
Abstract We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the ,1 and ,2 but not , receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an ,1 - or ,2 -adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by ,1 and ,2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate,serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems. [source]

Characterization of bovine neutrophil ,2 -adrenergic receptor function

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010
T. P. LaBRANCHE
LaBranche, T. P., Ehrich, M. F., Eyre, P. Characterization of bovine neutrophil ,2 -adrenergic receptor function. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01143.x. This study compares bovine leukocyte ,-adrenergic receptor densities to that of the rat, demonstrates for the first time a functional ,2 -adrenergic receptor signaling pathway in steer neutrophils, and investigates the effect of an inflammatory stimulus on that signaling pathway. The ,1 -/,2 -adrenergic antagonist [3H]CGP-12177 demonstrated that rat lymphocyte specific binding-site density was highest, followed by steer and dairy cow lymphocytes, and lastly steer and dairy cow neutrophils. The ,2 -adrenergic agonist terbutaline stimulated steer neutrophil adenosine 3,5-cyclic monophosphate (cAMP) production, an effect increased by inclusion of ,1 × 10,8 m phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. Both terbutaline and the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) independently decreased steer neutrophil superoxide anion production in a concentration-dependent manner, with 1 × 10,4 m IBMX enhancing both the potency and efficacy of the terbutaline effect (up to 74% reduction in superoxide anion production). Superoxide anion production was also reduced by the synthetic cAMP analog 8-bromo-cAMP, which increased the potency of the IBMX effect on superoxide anion production. Taken together, these data demonstrate the presence of a ,2 -adrenergic receptor signaling pathway in bovine neutrophils much like that described in other animal species, as well as the potential for an inflammatory stimulus to alter its function. [source]

Effects of chronic fluoxetine treatment in the presence and absence of (±)pindolol: a microdialysis study

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000
L A Dawson
Using in vivo microdialysis in the frontal cortex of the freely moving rat we evaluated the effects of chronic treatment with the serotonin specific reuptake inhibitor (SSRI) fluoxetine in the presence and absence of the 5-HT1A/,-adrenergic antagonist (±)pindolol. Chronic vehicle treated animals produced no significant response to a challenge with fluoxetine (10 mg kg,1) on day 8 and 15. Alternatively, a significant (P<0.05) decrease in extracellular 5-HT was observed in control animals upon challenge with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.03 and 0.1 mg kg,1). Conversely, animals treated with fluoxetine (10 mg kg,1 o.d.) for 7 and 14 days produced a significant (P<0.05) 2 fold increase in extracellular 5-HT when challenged with fluoxetine (10 mg kg,1) on day 8 and 15. Moreover, no significant decrease in extracellular 5-HT was observed upon challenge with either dose of 8-OH-DPAT. Animals chronically treated with (±)pindolol (10 or 20 mg kg,1 b.i.d.) produced a significant dose-related increase in extracellular 5-HT upon challenge with fluoxetine on day 15 only. Furthermore, both doses produced a significantly blunted response to the low dose challenge of 8-OH-DPAT (0.03 mg kg,1). In addition, 20 mg kg,1 (±)pindolol treated animals also had no response to the higher 0.1 mg kg,1 dose of 8-OH-DPAT. Animals treated for 14 days with a combination of (±)pindolol (10 or 20 mg kg,1) and fluoxetine were not significantly different from vehicle treated animals when challenged with fluoxetine or 8-OH-DPAT. Taken together it would therefore appear that although (±)pindolol alone has sufficient intrinsic activity to produce a desensitization of the 5-HT1A receptor, when given in combination with fluoxetine it is able to prevent the desensitization induced by not only fluoxetine but also itself. This may suggest that the clinical augmentation of antidepressant action by pindolol, when co-administered with a SSRI, is via antagonism of the 5-HT1A receptor. British Journal of Pharmacology (2000) 130, 797,804; doi:10.1038/sj.bjp.0703378 [source]

Psychosocial Stress Augments Tumor Development through ,-Adrenergic Activation in Mice

CANCER SCIENCE, Issue 7 2002
Hideo Hasegawa
Housing conditions affect behavioral and biological responses of animals. We investigated the effect of same-sex-grouped (G), crowded (GC) and isolated (I) conditions on the growth of B16 melanoma or Meth A fibrosarcoma implanted in the footpad of syngeneic male C57BL/6 or BALB/c mice. Differential housing altered host resistance to tumor growth. The host responses to stress were reflected in thymic atrophy, which was lowest in the G mice, highest in the GC mice and intermediate in the I mice. The GC condition was a more stressful social environment than the I condition in both male C57BL/6 and BALB/c mice. Reflecting the extent of psychosocial stress, tumor growth was augmented in the order of GC, I and G condition, and a negative mass correlation between tumor and thymus was observed, thus clearly indicating that the host resistance to tumors was attenuated by psychosocial stress. Furthermore, the stress-enhanced tumor growth and thymus atrophy were completely abrogated by the oral administration of the non-selective ,-adrenergic antagonist, propranolol. On the contrary, the chronic administration of corticosterone significantly induced the atrophy of thymus and spleen without affecting tumor growth. These results suggest an interrelationship among psychosocial stress, tumor growth and ,-adrenergic activation. [source]

Intrinsic vasomotricity and adrenergic effects in a model of isolated rabbit eye

ACTA OPHTHALMOLOGICA, Issue 4 2009
Esmeralda Delgado
Abstract. Purpose:, We aimed to investigate the responsiveness of the ocular arteries to adrenergic drugs in a model of perfused isolated rabbit eye. Methods:, Rabbit external ophthalmic arteries (n = 15) in a head-mounted preparation were cannulated and the retinal and uveal vasculature perfused at a constant flow with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and intraluminal pressure was taken as a measure of vascular resistance. Effects of intra-arterial injections of phenylephrine (group A, n = 5), prazosin (group B, n = 5) and phentolamine (group C, n = 5) on the recorded pressure were obtained. Student's paired- t test and one-way analysis of variance were used for statistical analysis (p < 0.05). Results:, Intrinsic vasomotricity was observed in all preparations prior to any drug administration. Phenylephrine produced an increase in total vascular resistance. Intrinsic vasomotricity became more evident, showing a lower frequency but higher amplitude of oscillations. Evoked vasomotor responses with phenylephrine (250 ,g/ml) were inhibited by intra-arterial administration of the selective ,1 -adrenergic antagonist, prazosin (0.5 mg/ml), as well as the non-selective ,-adrenergic antagonist phentolamine (6 mg/ml). Conclusions:, Rabbit external ophthalmic arteries showed spontaneous contractions under constant perfusion. Phenylephrine elicited a vasoconstrictor response that was inhibited by adrenergic antagonists. In addition, the intrinsic vasomotricity was enhanced by phenylephrine and blocked by adrenergic antagonists. These results show that under in vitro perfusion the territory presents similar responses to adrenergic drugs to those observed in in vivo models and also provides evidence of myogenic autoregulatory properties in the rabbit ophthalmic artery and/or choroid. [source]

Polymorphisms in the ,1A -adrenoceptor gene do not modify the short- and long-term efficacy of ,1 -adrenoceptor antagonists in the treatment of benign prostatic hyperplasia

BJU INTERNATIONAL, Issue 4 2006
CHAIDIR A. MOCHTAR
OBJECTIVE To determine whether a common single nucleotide polymorphism (SNP) in the ADRA1A gene encoding the ,1A -adrenoceptor modifies the short- and long-term efficacy of ,1 -adrenoceptor antagonists in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received ,1 -adrenergic antagonists for ,,3 months, the ADRA1A genotype at position 1475 of the coding region was determined. The patients' short-term response to treatment was determined for four outcome measures, i.e. the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score, peak urinary flow rate, and obstruction grade, stratified by genotype. Eventual BPH-related invasive therapy was used as the outcome for assessing the long-term response to treatment. Genetic variants at positions 834, 896, 898 and 1831 were too rare to be considered in the analysis. RESULTS There were no significant differences for the genotype strata in three of the four outcome measures. Patients with the CC genotype responded significantly better in quality-of-life perception than patients with the CT or TT genotype. There were also no significant differences in the risk of BPH-related invasive therapy among the three genotypes. CONCLUSIONS The 1475C,T SNP in the ADRA1A gene does not modify the short- and long-term efficacy of ,1 -adrenoceptor antagonists for treating BPH. There was a small effect on perceived quality of life but this was not reflected in other variables that measured the treatment response more directly. [source]

Myogenic bladder decompensation in boys with a history of posterior urethral valves is caused by secondary bladder neck obstruction?

BJU INTERNATIONAL, Issue 1 2005
Philippos A. Androulakakis
OBJECTIVE To investigate whether myogenic bladder decompensation in patients treated for congenital posterior urethral valves (PUV, the most serious cause of infravesical obstruction in male neonates and infants) may be secondary to bladder neck obstruction, as despite prompt ablation of PUV these patients can have dysfunctional voiding during later childhood or adolescence, the so-called ,valve bladder syndrome'. PATIENTS AND METHODS The study comprised 18 boys (mean age 14 years, range 6.2,18.5) who had had successful transurethral ablation of PUV between 1982 and 1996, and had completed a follow-up which included serial assessment of serum creatinine, completion of a standard voiding diary, ultrasonography with measurement of urine before and after voiding, a urodynamic examination with simultaneous multichannel recording of pressure, volume and flow relationships during the filling and voiding phases, coupled with video-cystoscopy at least twice. The mean (range) follow-up was 9.3 (6,17) years. RESULTS Urodynamic investigation showed myogenic failure with inadequate bladder emptying in 10 patients; five with myogenic failure also had unstable bladder contractions. On video-cystoscopy the posterior bladder neck lip appeared elevated in all patients but in those with myogenic failure it was strongly suggestive of hypertrophy, with evidence of obstruction. At the last follow-up one patient with myogenic failure who had had bladder neck incision and four others who were being treated with ,-adrenergic antagonists had a significant reduction of their postvoid residual urine. CONCLUSION Despite early valve ablation, a large proportion of boys treated for PUV have gradual detrusor decompensation, which may be caused by secondary bladder neck obstruction leading to obstructive voiding and finally detrusor failure. Surgical or pharmacological intervention to improve bladder neck obstruction may possibly avert this course, but further studies are needed to validate this hypothesis. [source]