OBJECTIVETo study the interactions between Ligusticum chuanxiong Hort extract and cardiac muscle membrane receptors.

METHODThe cell membrane of rabbit cardiac muscle was fixed on silicon to make cell membrane stationary phase (CMSP), and then the interactions were studied by comparing the retention characteristics of the extracts from different solvents with those of the antagonists or activators corresponding to known receptors in cardiac muscle membrane, and by competition effect on the retention characteristics of extracts when adding the antagonists or activators into the mobile phase.

RESULTWater extract and ethanol extract both had retentions on CMSP; the retention characteristics of water extract could be affected when water extract was in competition with the antagonists for alpha receptor, and could not be affected when with the activator beta1 receptor.

CONCLUSIONIt is possible that some components in water extract may combine with alpha receptor and no component with beta1 receptor, and that some components in ethanol extract may combine with cardiac muscle cell membrane. The process between active components and receptors in vivo can be imitated through the interactions between drugs and CMSP. The method provides references for the resolution of two applications: to screen the active components from Chinese medicine, and to figure out the type of receptors involved.

Adrenergic alpha-Agonists ; metabolism ; Adrenergic alpha-Antagonists ; metabolism ; Adrenergic beta-Agonists ; metabolism ; Adrenergic beta-Antagonists ; metabolism ; Animals ; Cell Membrane ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Ligusticum ; chemistry ; Male ; Myocytes, Cardiac ; cytology ; metabolism ; Plants, Medicinal ; chemistry ; Protein Binding ; Rabbits ; Receptors, Adrenergic, alpha ; metabolism ; Receptors, Adrenergic, beta ; metabolism

OBJECTIVEPostural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children.

DATA SOURCESThe data analyzed in this review are mainly from articles included in PubMed and EMBASE.

STUDY SELECTIONThe original articles and critical reviews about POTS were selected for this review.

RESULTSStudies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted.

CONCLUSIONSThe pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.

Adrenergic alpha-Agonists ; therapeutic use ; Adrenergic beta-Antagonists ; therapeutic use ; Catecholamines ; metabolism ; Humans ; Postural Orthostatic Tachycardia Syndrome ; drug therapy ; metabolism ; pathology ; therapy

OBJECTIVETo demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.

METHODSThe cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.

RESULTS(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.

CONCLUSIONNE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Animals, Newborn ; Cardiomegaly ; chemically induced ; pathology ; prevention & control ; Cell Enlargement ; drug effects ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; cytology ; Norepinephrine ; Prazosin ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

Adrenergic beta-2 Receptor Agonists ; pharmacology ; Anti-Inflammatory Agents ; pharmacology ; Asthma ; drug therapy ; physiopathology ; Chloroquine ; pharmacology ; Humans ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Quaternary Ammonium Compounds ; pharmacology ; Receptors, Adrenergic, beta-2 ; metabolism ; Receptors, G-Protein-Coupled ; agonists ; metabolism ; Receptors, Interleukin-4 ; antagonists & inhibitors ; metabolism ; Respiratory System ; drug effects ; metabolism ; physiopathology

There is evidence that the myocytes produce dynorphin and dynorphin-like peptides, which are kappa opioid receptor (kappa-OR) agonists. Activation of kappa-OR, a dominant opioid receptor in the heart, alters the cardiac function in vivo and in vitro. The observations suggest that the endogenous kappa-opioid peptides may act as autocrines or paracrine in regulation of cardiac functions. Myocardial ischemia is a common cause of heart disorders, which is manifested in decreased myocardial performance, arrhythmia and infarct. When myocardial ischemia occurs, the sympathetic discharge increases, which in turn increases the work-load and oxygen consumption. This exacerbates the situation induced by ischemia. One of the mechanisms with which the body protects against ischemia-induced injury/arrhythmia is inhibition of stimulation of beta-adrenoceptor (beta-AR), the receptor mediating the actions of sympathetic stimulation. kappa-Opioids inhibit the beta-AR activation. The inhibition of the beta-AR activation is due to inhibition of Gs-protein and to a lesser extent the adenylyl cyclase of the signaling pathway mediating beta-AR stimulation by a pertussis sensitive G-protein that mediates kappa-OR activation. Another mechanism against ischemia-induced injury is preconditioning, which is defined as prior exposures to ischemia or other insults make the heart more tolerant to subsequent and more severe insults. Protection occurs immediately or 1-3 days after preconditioning. kappa-OR mediates protection of preconditioning with ischemia or metabolic inhibition, one of the consequences of ischemia, in the heart. Activation of kappa-OR by U50488H, a selective kappa-OR agonist (pharmacological preconditioning with U50488H, UP), activates protein kinase C (PKC), opens K(ATP) channels and increases the production of heat shock proteins. Blockade of PKC, or closing of the K(ATP) channels or inhibition of the synthesis of the heat shock protein abolishes the cardioprotection of UP. The findings indicate the important roles of PKC, the K(ATP) channels and the heat shock protein in cardioprotection of UP. In addition, UP also attenuates the Ca(2+) overload, a precipitating cause of cardiac injury, induced by ischemic insults, indicating that UP may confer cardioprotection via at least partly attenuating the Ca(2+) overload. Most interestingly, blockade of the K(ATP) channels with channel blockers, that abolishes the delayed cardioprotection of UP, also attenuates the inhibitory effect of UP on Ca(2+) overload, suggesting that the cardioprotective effect of opening of the K(ATP) channels may be due at least partly to the prevention/attenuation of Ca(2+) overload.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Calcium ; metabolism ; Cardiotonic Agents ; Humans ; Ischemic Preconditioning, Myocardial ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Receptors, Adrenergic, beta ; physiology ; Receptors, Opioid, kappa ; agonists ; physiology ; Signal Transduction

After the approval and introduction of mirabegron, tadalafil, and botulinum toxin A for treatment of lower urinary tract symptoms/overactive bladder, focus of interest has been on their place in therapy versus the previous gold standard, antimuscarinics. However, since these agents also have limitations there has been increasing interest in what is coming next - what is in the pipeline? Despite progress in our knowledge of different factors involved in both peripheral and central modulation of lower urinary tract dysfunction, there are few innovations in the pipe-line. Most developments concern modifications of existing principles (antimuscarinics, beta3-receptor agonists, botulinum toxin A). However, there are several new and old targets/drugs of potential interest for further development, such as the purinergic and cannabinoid systems and the different members of the transient receptor potential channel family. However, even if there seems to be good rationale for further development of these principles, further exploration of their involvement in lower urinary tract function/dysfunction is necessary.
Adrenergic beta-3 Receptor Agonists/therapeutic use ; Botulinum Toxins, Type A/therapeutic use ; Drug Therapy, Combination ; Humans ; Molecular Targeted Therapy/methods/trends ; Muscarinic Antagonists/therapeutic use ; Neuromuscular Agents/therapeutic use ; Urinary Bladder, Overactive/*drug therapy

In acupuncture practice of animals, preanesthetics sometimes are needed. The purpose of this study was to select the ideal chemical restraint at acupuncture for gastric motility. Nine healthy mixed breed dogs weighed 10-21 kg and aged 1-3 years old were used in this study. Two EMG surface electrodes were placed between the seromuscular and the mucosal layer of pylorus. Twenty minutes after feeding normal gastric motility was recorded for 60 minutes using physiograph (Narco-Biosystem). Then preanesthetic treated-gastric motility was observed for 30 minutes. Preanesthetics used were xylazine, diazepam, and acepromazine. Acupuncture needles were inserted to BL-21 (Wei-Yu) acupoint, and then changes of gastric motility were recorded for 60 minutes. The gastric motility following xylazine administration (1 mg/kg, IV) was markedly decreased. BL-21 (Wei-Yu) acupoints stimulation did not alter xylazine-induced depression of gastric motility. The diazepam (1 mg/kg IV) treated-gastric motility was increased mildly 20 minutes after drug administration. BL-21 (Wei-Yu) acupoint stimulation after diazepam administration enhanced gastric motility significantly. The gastric motility following acepromazine (0.3 mg/kg, IM) administration was not changed compared with normal gastric motility. Application of traditional acupuncture at BL-21 (Wei-Yu) significantly increased the gastric motility. Based on these results, acepromazine and diazepam could be acceptable chemical restraints for acupuncture therapy of gastric motility, but xylazine couldn't be.
Acepromazine ; Acupuncture/*standards ; *Acupuncture Points ; Adjuvants, Anesthesia ; Adrenergic alpha-Agonists ; Animals ; Antipsychotic Agents ; Atropine ; Diazepam ; Dogs/*physiology ; Dopamine Antagonists ; Electromyography/veterinary ; Gastrointestinal Motility/drug effects/*physiology ; Hypnotics and Sedatives ; Metoclopramide ; Parasympatholytics ; Preanesthetic Medication/standards/*veterinary ; Xylazine

Urinary incontinence is an important lower urinary tract symptom that negatively affects the quality of life. Urgency incontinence (UI) is urine loss accompanied by urgency, which is the chief complaint of overactive bladder (OAB) syndrome. OAB is defined as urgency, with or without UI, usually with frequency and nocturia. In contrast, stress urinary incontinence (SUI) involves involuntary urine leakage caused by a sudden increase in abdominal pressure. Treatment for urinary incontinence depends on the type of incontinence, the severity, and the underlying causes. Treatment options fall into four broad categories: lifestyle intervention, bladder retraining and/or pelvic floor muscle training, pharmacotherapy, and surgery. Pharmacotherapy is often the first-line therapy for OAB/UI, either alone or as an adjunct to various nonpharmacological therapies. Effectiveness of anticholinergic drugs for OAB/UI has been assessed in various observational and randomized controlled trials. Despite their side effects, anticholinergics are the first-line agents for UI. Tricyclic antidepressants have complex pharmacological actions such as anticholinergic, alpha adrenergic, antihistaminic, and local anesthetic properties. Recently approved anticholinergics, solifenacin and darifenacin, are selective M3 antagonists that may have tolerable side effects. Transdermal oxybutynin may offer comparable efficacy with oral formulation but lower side effects. In the absence of an effective and well tolerated drug for SUI, pharmacological therapy for this condition has remained in the off-label prescription of some products, particularly estrogens and alpha-adrenergic agonists. Duloxetine is the drug of choice specifically aimed at SUI. This article outlines the current state and future development in pharmacological therapy for urinary incontinence.
Adrenergic alpha-Agonists ; Antidepressive Agents, Tricyclic ; Cholinergic Antagonists ; Drug Therapy ; Duloxetine Hydrochloride ; Estrogens ; Life Style ; Nocturia ; Pelvic Floor ; Prescriptions ; Quality of Life ; Solifenacin Succinate ; Urinary Bladder ; Urinary Bladder, Overactive ; Urinary Incontinence* ; Urinary Tract

The objective of this review is to propose the Korean practice guideline for pharmacological treatment of attentiondeficit hyperactivity disorder(ADHD). For making the guideline, the authors used the evidence-base approaches derived from a detailed review of literature including wide range of controlled clinical trials, studies of side effects of drugs, toxicological reports, and meta-analyses published in United States and Europe, as well as inside Korea. The review committee composed of experts in ADHD in Korea has reviewed the parameter. The practice parameter for pharmacological treatment describes the use of stimulants, atomoxetine, modafinil, bupropion, tricyclic antidepressants, and alpha-adrenergic agonists and their side effects. The recommendations of pharmacological treatment are proposed at the end of the article.
Adrenergic alpha-Agonists ; Advisory Committees ; Antidepressive Agents, Tricyclic ; Bupropion ; Europe ; Korea ; United States ; Atomoxetine Hydrochloride

beta -Blockers can cause bronchospasm in asthma. beta 2-agonists prolong the QT interval and alter the clinical course of long QT syndrome (LQTS). We report a case of asthma exacerbation treated cautiously with beta 2-agonists in a patient with LQTS, while LQTS was controlled with low-dose beta 1-antagonists. A 31-year-old woman with LQTS visited the emergency room for asthma exacerbation. FEV1 was 0.5 L (18%) and QTc interval was 520 ms. Low doses of salbutamol or salmeterol were used and gradually increased, while monitoring the QT interval. Simultaneously, a low dose of atenolol was maintained. FEV1 was increased to 2.2 L (83%) without further QT prolongation or cardiac events. The case suggests that lower doses of beta 1-antagonists can be tried for cardiac diseases, even in the presence of asthma exacerbations. beta 2-Agonists may be initiated at lower doses and, if tolerated, the dose can be increased in asthmatic patients with a risk for QT prolongation.
Adrenergic beta-Agonists ; Adrenergic beta-Antagonists ; Adult ; Albuterol ; Asthma ; Atenolol ; Bronchial Spasm ; Emergencies ; Female ; Heart Diseases ; Humans ; Long QT Syndrome ; Salmeterol Xinafoate