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Acta Crystallographica. Section C,... Apr 1998The title molecule, a hydrated hemisulfate salt of ethyl(2-methyl-1-phenyl-2-propyl)ammonium, C11H18N+.0.5SO4(2-).H2O, consists of a phenethylamine skeleton in which the...
The title molecule, a hydrated hemisulfate salt of ethyl(2-methyl-1-phenyl-2-propyl)ammonium, C11H18N+.0.5SO4(2-).H2O, consists of a phenethylamine skeleton in which the N atom is protonated. There are two molecules in the asymmetric unit, with the S atom of the SO4(2-) ion lying on a pseudo-twofold axis. The ethylamine side chain is in an extended conformation in both the symmetry-independent molecules. The distance of the N atom from the centre of the benzene ring is 5.1 A for molecule 1 and 5.3 A for molecule 2. The packing is stabilized by N-H...O and O-H...O hydrogen bonds.
Topics: Adrenergic Agents; Crystallography, X-Ray; Mephentermine; Models, Molecular; Molecular Structure
PubMed: 9604308
DOI: 10.1107/s0108270197015461 -
Journal of Clinical Hypertension Sep 1985The acute and chronic renal effects of the beta-adrenergic antagonists, alpha 1-adrenergic antagonists, central alpha 2-adrenergic agonists, and central and/or... (Review)
Review
The acute and chronic renal effects of the beta-adrenergic antagonists, alpha 1-adrenergic antagonists, central alpha 2-adrenergic agonists, and central and/or peripheral adrenergic-neuronal blocking agents are reviewed. In general, beta-adrenergic antagonists have little or no clinical effect on glomerular filtration rate (GFR), effective renal plasma flow or renal blood flow (ERPF/RBF), renal vascular resistance (RVR), urinary sodium or potassium excretion, free water clearance, or body fluid composition. The alpha 1-adrenergic antagonists (prazosin and indoramin) have little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Sodium excretion is also reduced, leading to salt and water retention. The central alpha 2-adrenergic agonists (alpha-methyldopa, clonidine, and guanabenz) have little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Urinary sodium and potassium excretion and body fluid composition are unchanged. Free water clearance may be increased. The central and peripheral adrenergic-neuronal blocking agent reserpine has little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Urinary sodium, potassium, and water excretion and body fluid composition are unchanged. Finally, the peripheral adrenergic-neuronal blocking agents (guanadrel and guanethidine) decrease GFR and ERPF/RBF; RVR is also reduced. The filtered load and fractional excretion of sodium is decreased, producing expansion of body fluid spaces and weight gain.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Body Water; Glomerular Filtration Rate; Guanethidine; Guanidines; Humans; Hypertension; Kidney; Plasma Volume; Potassium; Renal Circulation; Sodium; Vascular Resistance
PubMed: 2872278
DOI: No ID Found -
Molecules (Basel, Switzerland) Nov 2021Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety....
Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity. The newly synthesized compounds were tested in the radioligand binding assay and the intrinsic activity was evaluated for the selected derivatives. The computer-aided SAR analysis enabled us to answer questions about the influence of particular structural fragments on selective vs. multifunctional activity. As a result of the performed investigations, there were two leading structures: (a) compound with multifunctional adrenergic-serotonin activity, which is a promising candidate to be an effective anxiolytic agent; (b) compound with high α/α affinity and selectivity towards α, which is recommended due to the elimination of probable cardiotoxic effect The structural conclusions of this work provide significant support for future lead optimization in order to achieve the desired pharmacodynamic profile in searching for new CNS-modulating agents.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Anti-Anxiety Agents; HEK293 Cells; Humans; Molecular Structure; Piperazines; Rats; Receptors, Adrenergic, alpha-1
PubMed: 34834117
DOI: 10.3390/molecules26227025 -
The Journal of Pharmacology and... Feb 1947
Topics: Adrenergic Antagonists; Dibenzylchlorethamine; Ethylamines
PubMed: 20285837
DOI: No ID Found -
Cutis Jun 1976The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a... (Review)
Review
The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a high degree of specificity for the lung and few cardiac and central nervous system stimulating problems. These agents are useful by aerosol and oral routes, alone and in addition to theophylline for asthma. Theophylline, which acts to increase cyclic AMP by inhibition of phosphodiesterase and beta 2 adrenergic agents which increase cyclic AMP by stimulating adenylate cyclase, are the mainstays of asthma therapy. Therapy is usually begun with theophylline. Persistent symptoms with adequate theophylline levels (10-20 mug/ml) indicates the need for a beta 2 adrenergic agent by aerosol or orally as a supplement. Occasional patients will not tolerate theophylline in any preparation and can be treated with beta 2 adrenergic agents with success. The future holds great promise for improved and safer beta 2 adrenergic agents which will offer the physician a more effective means of treating asthma.
Topics: Adrenergic beta-Agonists; Adult; Asthma; Chemical Phenomena; Chemistry; Child; Humans; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Stimulation, Chemical; Sympathomimetics; Theophylline
PubMed: 13964
DOI: No ID Found -
European Journal of Psychotraumatology 2024Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic... (Review)
Review
Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD. PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented. Ten reports, accounting for = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications. Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.
Topics: Clonidine; Humans; Stress Disorders, Post-Traumatic; Dreams; Sleep Quality; Adrenergic alpha-2 Receptor Agonists
PubMed: 38941125
DOI: 10.1080/20008066.2024.2366049 -
Journal of Cardiovascular Pharmacology 1984Centrally acting agents and the beta-adrenergic antagonists represent two classes of antihypertensive agents recommended for initial monotherapy. Comparisons of the... (Comparative Study)
Comparative Study
Centrally acting agents and the beta-adrenergic antagonists represent two classes of antihypertensive agents recommended for initial monotherapy. Comparisons of the efficacy and safety of the centrally acting agent, guanabenz, with those of propranolol and pindolol in patients with mild to moderately severe hypertension, are reported. In the guanabenz versus propranolol study, mean supine blood pressure decreased by 19/15 mm Hg for 44 guanabenz-treated patients and by 17/15 mm Hg for 52 propranolol-treated patients who completed 6 months of therapy. In the guanabenz versus pindolol study, the mean decrease in supine blood pressure was 17/14 mm Hg for the 12 patients treated with guanabenz and 21/15 mm Hg for the 13 patients who received pindolol and completed 2 months of therapy. If the patients who discontinued therapy for drug-related reasons are considered, the percentages of patients with clinically satisfactory blood pressure reductions were 59% for the guanabenz group versus 62% for the propranolol group and 79% for guanabenz-treated patients versus 64% for pindolol-treated patients. Although adverse effects, including dry mouth, drowsiness, and weakness, were more common among guanabenz-treated patients, these effects generally were mild and became less frequent with continued therapy. The therapeutic efficacy and safety of guanabenz were similar to those of the two beta-adrenergic blocking drugs, propranolol and pindolol. Guanabenz therapy decreased serum total cholesterol (p less than 0.05), whereas propranolol therapy decreased HDL cholesterol (p less than 0.05). Thus, guanabenz did not produce serum lipid abnormalities that may be associated with increased cardiovascular risk.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Blood Pressure; Female; Guanabenz; Humans; Hypertension; Male; Middle Aged; Pindolol; Potassium; Propranolol; Pulse; Time Factors
PubMed: 6084130
DOI: 10.1097/00005344-198400065-00016 -
American Journal of Hypertension Feb 1989While there is general agreement on the natural history, pathology, and pathophysiology of hypertension, there continues to be controversy over the selection of specific... (Review)
Review
While there is general agreement on the natural history, pathology, and pathophysiology of hypertension, there continues to be controversy over the selection of specific antihypertensive agents. All antihypertensive agents will, by definition, lower blood pressure, and factors beyond side effects and other difficulties associated with therapy form the basis of selecting specific agents. One of these factors is the effect of a given drug on core organ function. Propranolol was the first beta-adrenoceptor-blocking agent introduced for the treatment of hypertension. Initiation of therapy with propranolol may result in a decline in blood pressure more at the expense of cardiac function due to a concomitant rise in total peripheral resistance. Furthermore, propranolol may result in a decline in both glomerular filtration rate (GFR) and renal blood flow (RBF). In contrast, cardioselective beta-blockers or those with intrinsic sympathomimetic activity may not adversely affect renal function. It had been predicted that nadolol, a noncardioselective beta-blocker without intrinsic sympathomimetic activity, should result in decreased renal function. In contrast, observations demonstrated a preservation or improvement in both RBF and GFR, suggesting the presence of an alternative effective mechanism. Recent additions to the beta-adrenolytic group of antihypertensive agents include drugs with concurrent beta-blockade and vasodilation. This vasodilatation may be achieved through agonist properties resulting in lesser increases in vasomotor tone and smaller, if any, decreases in cardiac output. Alternatively, vasodilation may be achieved by concomitant alpha-adrenoceptor blockade, such as with labetalol. This agent preserves GFR and RBF during therapy of hypertension, in patients with normal as well as diminished renal function and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adrenergic beta-Antagonists; Glomerular Filtration Rate; Humans; Hypertension
PubMed: 2563944
DOI: 10.1093/ajh/2.2.86s -
Cardiovascular Research Aug 2022Heart failure (HF) is characterized by an overactivation of β-adrenergic signalling that directly contributes to impairment of myocardial function. Moreover,...
AIMS
Heart failure (HF) is characterized by an overactivation of β-adrenergic signalling that directly contributes to impairment of myocardial function. Moreover, β-adrenergic overactivation induces adipose tissue lipolysis, which may further worsen the development of HF. Recently, we demonstrated that adipose tissue-specific deletion of adipose triglyceride lipase (ATGL) prevents pressure-mediated HF in mice. In this study, we investigated the cardioprotective effects of a new pharmacological inhibitor of ATGL, Atglistatin, predominantly targeting ATGL in adipose tissue, on catecholamine-induced cardiac damage.
METHODS AND RESULTS
Male 129/Sv mice received repeated injections of isoproterenol (ISO, 25 mg/kg BW) to induce cardiac damage. Five days prior to ISO application, oral Atglistatin (2 mmol/kg diet) or control treatment was started. Two and twelve days after the last ISO injection cardiac function was analysed by echocardiography. The myocardial deformation was evaluated using speckle-tracking-technique. Twelve days after the last ISO injection, echocardiographic analysis revealed a markedly impaired global longitudinal strain, which was significantly improved by the application of Atglistatin. No changes in ejection fraction were observed. Further studies included histological-, WB-, and RT-qPCR-based analysis of cardiac tissue, followed by cell culture experiments and mass spectrometry-based lipidome analysis. ISO application induced subendocardial fibrosis and a profound pro-apoptotic cardiac response, as demonstrated using an apoptosis-specific gene expression-array. Atglistatin treatment led to a dramatic reduction of these pro-fibrotic and pro-apoptotic processes. We then identified a specific set of fatty acids (FAs) liberated from adipocytes under ISO stimulation (palmitic acid, palmitoleic acid, and oleic acid), which induced pro-apoptotic effects in cardiomyocytes. Atglistatin significantly blocked this adipocytic FA secretion.
CONCLUSION
This study demonstrates cardioprotective effects of Atglistatin in a mouse model of catecholamine-induced cardiac damage/dysfunction, involving anti-apoptotic and anti-fibrotic actions. Notably, beneficial cardioprotective effects of Atglistatin are likely mediated by non-cardiac actions, supporting the concept that pharmacological targeting of adipose tissue may provide an effective way to treat cardiac dysfunction.
Topics: Adipose Tissue; Adrenergic Agents; Animals; Catecholamines; Heart Failure; Lipase; Lipolysis; Male; Mice; Phenylurea Compounds
PubMed: 34061169
DOI: 10.1093/cvr/cvab182 -
Journal of Visualized Experiments : JoVE May 2021Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments...
Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments on the heart. Due to the feasibility of genetic manipulations the mouse has become the most common mammalian animal model to study cardiac function and to search for new potential therapeutic targets. Here we describe a protocol to determine cardiac function in vivo using pressure-volume loop measurements and analysis during basal conditions and under β-adrenergic stimulation by intravenous infusion of increasing concentrations of isoproterenol. We provide a refined protocol including ventilation support taking into account the positive end-expiratory pressure to ameliorate negative effects during open-chest measurements, and potent analgesia (Buprenorphine) to avoid uncontrollable myocardial stress evoked by pain during the procedure. All together the detailed description of the procedure and discussion about possible pitfalls enables highly standardized and reproducible pressure-volume loop analysis, reducing the exclusion of animals from the experimental cohort by preventing possible methodological bias.
Topics: Adrenergic Agents; Adrenergic beta-Agonists; Animals; Heart; Isoproterenol; Mice; Myocardial Contraction; Myocardium
PubMed: 34096910
DOI: 10.3791/62057