Tolerability of fentonium bromide in Indonesian volunteers

Summary

A double-blind crossover trial was carried out in 24 healthy Indonesian volunteers to assess the incidence of atropine-like side-effects after a single oral 80?mg dose of fentonium bromide compared with that after a single oral 80?mg dose of hyoscine-N-butyl bromide, and of placebo. Assessments of side-effects were made on subjective responses and objective measurements taken before, 2 hours, and 4 hours after administration of the drugs. The results showed that fentonium bromide did not produce significant atropine-like side-effects. Uyoscine-N-butyl bromide, however, did have a slight effect on pulse rate, although not of significance clinically, and produced a statistically significant, transient decrease in salivation.     

Relative Potency of the Atropine-Like Effects of A New parasympatholytic Drug,Scopolamine-N-(Cyclopropy 1 Methyl) Bromide and Those of Hyoscine-N-Butyl Bromide

Summary

A Double-Blind Crossover Trial With A 4-Point Bioassay Was Carried Out In 8 Convalescent In-Patients To Study The Relative Potency Of Scopolamine-N-(Cyclopropyl Methyl) Bromide (Da 3177), A New parasympatholytic Drug, Administered At Doses Of 2.5?mg And 5?mg I.V., And Hyoscine-N-Butyl Bromide, Administered At Doses Of 10?mg And 20?mg I.V., In Producing Atropine-Like Effects. The Results Showed That The Effects On Heart Rate And Near Point Of Accommodation Were Slightly Less With Da 3177, While Its Effects On Salivary Secretion Were A Little Greater Than Those Of Hyoscine-N-Butyl Bromide. It Is Suggested That Study Of The Pharmacodynamic Effects Of parasympatholytic Drugs Is A Relatively Simple Way Of Predicting Which Doses Should Be Effective Spasmolytically.     

The use of flavoxate in cystitis and renal colic

Summary

Two double-blind trials and one open study were carried out to assess the efficacy of the spasmolytic, flavoxate, in relieving the pain and discomfort associated with various urological conditions. In the first two studies, 24 patients with renal colic and 34 with cystitis or urethrotrigonitis were treated orally with either 0.2?g. flavoxate t.d.s. or placebo. In the open study, 25 patients with acute renal colic were given a single i/v injection of flavoxate (0–1?g.).

Thirty-four (68 %) of the 54 patients receiving flavoxate showed a good or moderate response in terms of symptom relief compared with only 8 (28%) of the patients on placebo. The results of cystometrography in 7 patients on flavoxate and 7 on placebo showed that the increase in bladder capacity and the reduction in pressure after flavoxate treatment were statistically significant but not so in the case of placebo. No side-effects or adverse reactions were noted in any of the patients treated.     

Physiological conditions controlling the activity of an orally administered parasympatholytic drug: Hyoscine-N-butylbromide

Summary

The author reviews the experimental evidence relating to the activity of orally administered parasympatholytic drugs and comments that the effectiveness, especially of those with spasmolytic activity, can only be judged if allowance is made for the physiological and pharmacodynamic conditions at the target site.

Using hyoscine-N-butylbromide as an example it has been shown that, apart from a local effect on the gut wall, therapeutic effects on muscular organs are possible and even at very low blood levels, below the limit of detection in the systemic circulation, if the site of action has a special affinity for the drug. The absence of anticholinergic side-effects and low rates of absorption into the blood cannot disprove the effects of drugs which are accumulated at the site of action. The combination of specific binding capacity and reactivity of the smooth musculature to hyoscine-N-butylbromide is to be regarded as the optimum condition for a specific therapeutic action. Opposite conclusions are drawn whenever either the experimental design fails to take account of the muscular activity or when the absorption rate is overestimated and, simultaneously, the accumulation of the drug in the target organ is not considered     

盐酸丙哌维林对膀胱平滑肌收缩的影响(英文)

观察了盐酸丙哌维林 ( Pro)对离体豚鼠膀胱平滑肌自动节律性收缩和 KCl诱导离体豚鼠膀胱平滑肌收缩的影响 ;同时观察了 Pro对家犬在体膀胱自动节律性收缩的影响 .Pro在 1 ,1 0 μmol· L-1浓度时 ,对离体豚鼠膀胱平滑肌自动节律性活动具有兴奋作用 ,可使自动节律性收缩频率增加 ,幅度加大 ;在 1 0 0μmol· L-1浓度时则表现为抑制作用 ,可完全抑制豚鼠膀胱平滑肌的自动节律性收缩 ,同时可使平滑肌松弛 ,基础张力降低 .Pro对 KCl引起的豚鼠离体膀胱平滑肌的收缩具有明显的抑制作用 ,在 1 ,1 0 ,1 0 0 μmol· L-1浓度时对 KCl诱导豚鼠离体膀胱平滑肌收缩的抑制率分别为 ( 7.4±6.5) % ,( 31 .3± 1 2 .8) % ,( 68.4± 7.1 ) % ,其 IC50 为( 2 5.2± 4.7) μmol·L-1.十二指肠给 Pro对在体家犬膀胱自动节律性收缩具有明显的抑制作用 ,60 ,30mg· kg-1可明显降低膀胱自动节律性收缩频率和幅度且具有剂量依赖性 ,与药前比有显著性差异 ,60 mg· kg-1药后 1 0 min即可起效 ,药效可持续 90min,Pro在上述剂量下对血压 ,心率无明显影响 .本实验结果提示 Pro在低剂量时对离体膀胱自动节律性收缩具有一定的兴奋作用 ,在高剂量时则表现为明显的抑制作用 ;Pro对 KCl诱导的豚鼠离体膀胱平滑肌收缩和膀胱扩张诱导的家?     

Absorption of14C-methylscopolamine from the digestive tract

Summary ¹⁴C-methylscopolamine (1.5 or 15 mg) and the non-absorbable markers polyethylene glycol or¹²⁵I-polyvinyl pyrolidon were taken by mouth or infused directly into the duodenum or the upper jejunum of 8 healthy subjects. Comparison of the radioactivity per unit quantity of marker in intestinal aspirates and in the test solution (A/T ratio) showed that about 20 per cent or less of the label was absorbed during its passage through the upper part of the small intestine. Very small amounts of¹⁴C-radioactivity were found in the plasma. Over a 7-day period the urinary excretion of label amounted to 7–15 per cent of the dose given. The A/T ratios and urinary excretion of¹⁴C-radioactivity showed that there was no consistent relation between the absorption of¹⁴C-label and the dose of methylscopolamine administered or the type of non-absorbable marker used. There was no evidence of breakdown of the drug in the upper small intestine. — In a 9th subject, labelled methylscopolamine was instilled into the middle part of the jejunum. The yield of¹⁴C-radioactivity in the urine was only 2.6 per cent, which indicates very poor absorption of the drug from the distal jejunum, ileum or colon.     

Ileal J-Pouch-Anal Anastomosis,Sexual Dysfunction,and Fertility

Background: Our aim was to establish what kind of changes take place in sexual functions after restorative proctocolectomy and ileoanal anastomosis with J-pouch (IAA) and whether the operation alters fertility. Methods: One hundred and ten consecutive patients who underwent IAA operation for ulcerative colitis at our institute were sent a questionnaire after at least 2 years' follow-up with special emphasis on sexual functions. Analysis was made by an independent researcher. Results: Ninety-five patients (86.7%) responded to the questionnaire. The mean follow-up of the patients was 71.5 months (range, 30-128 months). The median age of the 51 women in this study was 39.0 years (range, 23-74 years). Dyspareunia increased after the operation, but sexual satisfaction improved. The operation seems to reduce fertility slightly in women, and the rate of spontaneous abortion may be higher than in the normal population. The median age of the men was 43.0 (25-69) years. One (2.3%) case of retrograde ejaculation and six (14.6%) cases of erectile function problems were reported after the operation. The fear of leakage during coitus were reduced. Conclusions: Sexual satisfaction is improved after operation, mainly due to improved general health, despite minor disturbances in sexual function. There may be a risk of decreased fertility after restorative proctocolectomy.     

3-(2-羟基-2-环戊基-2-苯基-乙氧基)奎宁环烷及其光学异构体与外周毒蕈碱性受体的结合特性

采用放射性配体-受体结合实验, 研究了3-(2-羟基-20环戊基-2-苯基-乙氧基)奎宁环烷 (PCHEQ)及其4个光学异构体对豚鼠心脏, 小肠纵肌, 颌下腺和猪虹膜中的M受体的作用. 结果表明, 4种组织中的M受体对PCHEQ及其异构体表现出相似的立体选择性. PCHEQ及其异构体对4种组织中M受体的亲和力顺序相同,即RR′>PCHEQ>SR′>RS′>SS′. 这些化合物对颌下腺中的M受体的选择性较高, 尤以SR′异构体为显著.     

新型抗胆碱药物盐酸戊乙奎醚及其4种光学异构体对N受体离子通道的作用

在非洲爪蟾培养的胚胎神经元和骨骼肌细胞上, 本文采用细胞膜片钳技术, 研究新型抗胆碱能药物盐酸戊乙奎醚(PHC)及其4种光学异构体对骨骼肌细胞N受体离子通道的作用. 结果表明PHC可阻断神经肌肉接头乙酰胆碱传递; 其4种光学异构体与之相比在对抗强度上无明显差别. PHC优先阻断开放时间长、电流强度大的N受体通道. 此外, PHC及其4种光学异构体对钠和钾离子通道也具有一定强度的阻断作用.