Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

舒喘灵气雾剂治疗毛细支气管炎临床观察

目的 探讨舒喘灵气雾剂对毛细支气管炎的治疗效果。方法 选择106例住院毛细支气管炎患儿随机分为两组,对照组给予常规治疗,治疗组在常规治疗的基础上给予舒喘灵气雾剂,每天3次吸入。疗程结束后,观察毛细支气管炎改善情况。结果 治疗组有效率90％,对照组有效率17.4％,两组对比P<0.01,差异显著。结论 舒喘灵气雾剂对毛细支气管炎治疗效果佳,副作用小,值得推广。     

The biochemical effects of high-dose inhaled salbutamol in patients with asthma

Summary We have studied the biochemical effects of high doses of inhaled salbutamol in 14 asthmatic patients age 38 years, FEV₁ 62%. Cumulative doubling doses of inhaled salbutamol were given every 20 min as follows: 100 µg, 200 µg, 500 µg, 1000 µg, 2000 µg, 4000 µg. Plasma glucose, potassium, and magnesium were measured at each step of the doseresponse curve.Salbutamol produced significant hypokalaemic and hyperglycaemic effects, but no significant change in magnesium. There were linear log-dose responses for both glucose (r/it=0.58) and potassium (r=–0.46).There were wide individual variations in maximum responses to salbutamol 4000 µg (as means and 95% confidence intervals): glucose 1.46 (0.83 to 2.09) mmol/l, potassium –0.38 (–0.64 to –0.12) mmol/l.Thus, hypokalaemic and hyperglycaemic effects may occur with doses of salbutamol similar to those curently used for nebulizer therapy (2.5–5 mg). We postulate that during acute exacerbations of airflow obstruction these changes may be accentuated and become clinically relevant.     

沙丁胺醇加布地奈德微量泵吸入治疗小儿毛细支气管炎的疗效观察

目的 :评价沙丁胺醇 (喘乐宁 )加布地奈德 (普米克令舒 )微量泵吸入治疗小儿毛细支气管炎的疗效。方法 :随机将 72例患儿分为两组。对照组在综合疗法基础上单用喘乐宁微量泵吸入治疗 ,治疗组加用喘乐宁及普米克令舒微量泵吸入治疗。观察两组疗效及气急缓解和喘鸣音消失时间。结果 :显效率治疗组为 94.4% ,对照组为 72 .2 % ,两者相比有显著性差异 ( χ2 =4.9,P <0 .0 5 ) ;治疗组气急缓解、喘鸣音消失时间均较对照组短。结论 :喘乐宁加普米克令舒微量泵吸入治疗小儿毛细支气管炎较单用喘乐宁有较好疗效。     

Dose-response comparison of broxaterol and salbutamol pressurized aerosols

Summary The bronchodilating activity and tolerability of broxaterol and salbutamol administered by pressurized metered dose inhalers have been compared in 9 adult patients with bronchial asthma and clinically stable and reversible bronchospasm. Placebo was used as a control. On 3 different days broxaterol and salbutamol in cumulative doses of 100, 200 and 400 g and placebo were administered every 30 min according to a double-blind, Latin-square design.After each dose of broxaterol and salbutamol the increases in FVC and FEV₁ were always significantly larger than after placebo. Broxaterol at the doses tested induced a bronchodilator response which depended on the dose according to a relation not significantly different from a straight line, and with a potency at least comparable to that of salbutamol. The tolerability of the two drugs was good: only in 1 patient were slight tremors observed after the highest dose of each drug.The bronchodilating activity and the tolerability of broxaterol were not significantly different from those of salbutamol at the same doses.     

色甘胺醇气雾剂的高效液相色谱测定法

目的： 建立高效液相色谱法同时测定色甘胺醇气雾剂中的２ 个有效成分色甘酸钠和硫酸沙丁胺醇。方法： 采用Ｃ１８ 色谱柱, 以０－０２ ｍｏｌ·Ｌ－ １ 醋酸铵（ 用冰醋酸调节ｐＨ 为６－０ ±０－１） － 甲醇（１００∶３０） 为流动相, 检测波长为２２７ ｎｍ－ 结果： 色甘酸钠和硫酸沙丁胺醇的平均回收率（ ｎ ＝ ５）分别为９９－１２ ％ 和９９－９８ ％ ; 精密度（ ＲＳＤ） 分别为１－１ ％ 和１－０ ％ 。结论： 该测定方法简便快速     

Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

Acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma

Abstract A review of the literature highlights the need for research, particularly on the acute bronchodilatory effect of salmeterol on bronchoconstriction in the pediatric age group. The present study attempted to evaluate the acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma and to compare it with the effect of salbutamol. Forty-four asymptomatic children with mild-to-moderate asthma (23 boys and 21 girls; aged7–17 years) were studied. At the beginning, the baseline forced expiratory volume in 1 s (FEV₁) was measured, and the methacholine challenge was performed by doubling the dose to determine PC₂₀ (provocative concentration of inhaled methacholine required to reduce FEV! by 20%). At the same time, the transcutaneous arterial oxygen saturation (S_ao₂) was also measured. Each subject inhaled a single dose of 25 μ salmeterol (n: 23, group I) or 100 μg salbutamol (n: 21, group II) following the Sp₂ measurement. The same measurements (FEV₁, S_ao₂) were repeated 5 and 20 min after the inhalation. After inhalation of salmeterol or salbutamol, the differences between the values of FEV₁ and S_aO₂ after 5 and 20 min were insignificant in both group I and group II (P > 0.05), although there was a significant improvement in both FEV₁ and S_aO₂ after 5 and 20 min (P < 0.005). From these findings it was concluded that salmeterol can be considered as effective as salbutamol on methacholine-induced bronchoconstriction.     

Salbutamol or mist in acute bronchiolitis

Abstract Background : The role of bronchodilators in the treatment of bronchiolitis remains controversial.
Methods : A double-blind, placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol. One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were randomized to three groups as follows: (i) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline; (ii) saline was nebulized to 52 patients in group II and (iii) in group III 52 patients received mist in a tent. All three groups were administered oxygen during the procedures. Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more. Respiratory rate, heart rate, oxygen saturation and presence of cyanosis, wheezing, retractions were recorded before and after each treatment.
Results : The decrease in the respiratory score was 5.2 ± 1.8, 0.82 ± 2.4 and 1.7 ± 1.3 in group I, II and III, respectively. The decrease in group I was significantly higher than in the other groups. Heart rate was similar between groups. Oxygen saturation decreased in group I without reaching statistical significance.
Conclusions: Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis.     

荧光分光光度法测定硫酸沙丁胺醇注射液的含量

目的:建立荧光分光光度法测定硫酸沙丁胺醇注射液的含量.方法:将样品稀释后,以280 nm为激发波长,310 nm为发射波长,狭缝5 nm.结果:硫酸沙丁胺醇在2～140μg/mL浓度范围呈现良好的线性关系.回归方程为y=2.378 8 C 66.857,r=0.999 6,平均回收率为99.3%,RSD=0.85%(n=5).结论:该法简便易行、灵敏度高、重现性好,可用于硫酸沙丁胺醇注射液的含量测定.