Drug induced esophageal lesions studied in vitro.

This paper describes an in vitro method of studying the esophago-irritant potential of oral formulations of drugs. Porcine esophagus was used. The method offers the possibility of studying muscle activity and enzyme leakage (e.g. LDH) and of performing histomorphology of the exposed preparations. Examples of drugs which were tested are alprenolol (Aptin), propranolol (Inderal), doxycycline (Idocyklin) and (Vibramycin) and emepronium bromide (Cetiprin). Concerning effects on muscle activity, Aptic caused a marginal contraction while Cetiprin caused a relaxation of the esophagus preparation. Increased LDH-leakage was noted during exposure with the above mentioned pills in comparison with concurrent control preparations. Histopathological examination disclosed morphological changes such as softening and necrosis of the squamous epithelium of the esophageal mucosa after exposure to drugs like Idocyklin and Aptin.

Relationship between gastric emptying and serum concentrations of emepronium in dogs and human volunteers.

Clinical trials with increased dosages, relative to the standard regimen, of the anticholinergic drug emepronium (Cetiprin Novum) resulted in a clear improvement in micturition- and urodynamic parameters in urinary incontinent patients. In the present study possible effects on the gastric emptying were tested in dogs and in human volunteers. In dogs a wide dose range of emepronium (5-100 mg/kg p.o.) was used to establish a relationship between serum concentration and effect on the gastric emptying. Gastric emptying was slightly decreased after 25 mg/kg (peak conc. of emepronium about 100 micrograms/l) and markedly decreased after 50 mg/kg (500 micrograms/l) and 100 mg/kg (5000 micrograms/l). In the volunteers no effect of emepronium on gastric emptying was observed, either after 200 mg q.i.d. or after 400 mg q.i.d. (about 3 and 6 mg/kg q.i.d.), which resulted in peak serum concentrations of 100-300 micrograms/l).

[Treatment of motor dysfunction of the urinary bladder]. / Therapie der motorischen Reizblase.

Symptoms and objective characteristics of 86 female patients with bladder instability and uninhibited detrusor contractions suffering from urgency incontinence were analyzed. The subjective and objective response to a six week-parasympathicolytic treatment with Emepronium-Bromide (Cetiprin) was examined and the results are discussed.

Anticholinergic drugs, buccal ulceration and mucosal potential difference.

Measurement of changes in buccal mucosal potential difference produced by contact with drug formulations may provide a means of predicting their mucosal toxicity and ulcerogenic activity.

Uropharmacology: VII. Ganglionic stimulating and blocking agents.

A classification of the various ganglionic stimulants and blockers is presented, and their pharmacologic effects on the urinary bladder and urethra are discussed. Ganglionic stimulating drugs are of considerable interest in investigational work but are not presently used therapeutically. Ganglionic blockers include hexamethonium, tetraethylammonium, mecamylamine emepronium, pentolinium, chlorisondamine, and pemipidine. Of the numerous ganglionic blocking drugs that have appeared on the therapeutic scene, only mecamylamine, pentolinium, and trimethaphan are currently official.

A second look at emepronium bromide in urinary incontinence.

Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.

The effects of some anticholinergic compounds on the rabbit ureter.

Atropine, emeprone, and PR 197--a new anticholinergic compound--were examined for their possible effects on the rabbit ureter in situ. Ureteral pressure, recorded at two levels simultaneously, and intravesical pressure were studied. The effects of the substances were recorded in both normal (unobstructed) and obstructed ureters. It was found that all the substances, but especially PR 197, produced a fall in the basic intra-ureteral pressure, which was most pronounced in animals with obstructed ureters. PR 197 also temporarily abolished the ureteral peristalsis, while atropine and emeprone did not have this effect.

The effects of emeprone on intravesical and intra-urethral pressure in women with urgency incontinence.

By use of a sensitive technique, simultaneous registration of intravesical and intra-urethral pressure changes was performed in 14 patients with urgency incontinence before and after intramuscular or oral administraiton of emeprone. The serum concentrations of the drug at different times after administration were also measured. After intramuscular injection, emeprone caused an increased bladder capacity in all the patients, and they experienced urge at larger bladder volumes. The urethral pressure was little affected. Thus, there were no significant changes of the maximum urethral pressure or of the functinal length of the urethra. Eight out of nine patients got a residual urine. After oral administration of emeprone, two out of five patients got an increased bladder capacity, and experienced urge at a larger bladder volume. They had no residual urine. In the patients receiving emeprone intramuscularly, the maximum plasma concentrations ranged from 1171 ng/ml to 378 ng/ml; they were found after 15 or 30 min. After oral intake, the maximum concentrations ranged from 36 ng/ml to 64 ng/ml and were found after 60 to 180 min. The results suggest that emeprone has actions mainly on the bladder; the effects on the urethra seem to be small.

Emepronium bromide (Cetiprin) as a postoperative spasmolytic agent in transvesical prostatectomy.

To find out whether Cetiprin reduces the vesical spasms seen after cystotomias, a double-blind investigation including 22 men was carried out. Eleven of the men were given 25 mg Cetiprin i.m. twice a day for 2 days after transvesical prostatectomy, then 200 mg orally 3 times a day the following 12 days. The rest of the men, 11 patients, received placebo. In the Cetiprin group 9 patients had no vesical spasm postoperatively, whereas 1 had moderate and 1 had severe spasms. Only 4 patients were without spasms in the control group, whereas 5 had moderate and 2 severe spasms. The postoperative reduction of the bladder volume were counteracted by Cetiprin. No significant influence on liver- or kidney function was seen with the dosages mentioned.

An urodynamic study of emepronium bromide in bladder dysfunction.

The effect of emepronium bromide in 13 patients, most of whom had uninhibited bladders, has been studied urodynamically. Under the influence of this drug, the detrusor pressure and the urinary flow was reduced, and abdominal straining during during micturition was commonly recorded. The bladder capacity increased considerably, but all subjects developed residual urine. The effect of emepronium bromide on the bladder capacity seemed to last for a longer period than the effect on the detrusor pressure.