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Review article: botulinum toxin in the therapy of gastrointestinal motility disorders.

Since 1980, botulinum toxin has been employed for the treatment of various voluntary muscle spastic disorders in the fields of neurology and ophthalmology. More recently, botulinum toxin has been proved to be effective in the therapy of dyskinetic smooth muscle disorders of the gastrointestinal tract. Achalasia and anal fissure are the gastrointestinal disorders in which botulinum toxin therapy has been most extensively investigated. Botulinum toxin is the best treatment option for achalasia in patients whose condition makes them unfit for pneumatic dilation or surgery. In anal fissure, botulinum toxin is highly effective and may become the treatment of choice. In the future, botulinum toxin application in the gastrointestinal tract will be extended to many other gastrointestinal disorders, such as non-achalasic motor disorders of the oesophagus, dysfunction of Oddi's sphincter, achalasia of the internal anal sphincter and others. This article describes the mechanism of action, rationale of employment, indications and side-effects of botulinum toxin application in smooth muscle disorders of the gastrointestinal tract, and compares the results of different techniques of botulinum toxin therapeutic application.

Anti-Dyskinesia Agents↗

Discovery of a potent, peripherally selective trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonist for the treatment of gastrointestinal motility disorders.

Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (Ki = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (> 200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.

Animals↗

[Gastrointestinal motility disorders in late stages of adhesive intestinal obstruction in children].

The results of examination and treatment of 211 patients with late adhesive ileus (LTAI) are discussed. Highly sensitive noninvasive method of phonoenterography was used for LTAI diagnosis and control of the efficacy of non-operative treatment. The gastrointestinal motor-evacuation disorders were studied in a group of patients with chronic recurring LTAI. For revealing hypertension in the upper parts of the gastrointestinal tract, a special catheter is suggested by means of which the pressure in the gastric and duodenal cavities can be measured simultaneously. The suggested examination methods allowed a differentiated approach to the choice of the therapeutic tactics, objective control over the efficacy of the treatment, and substantiation of the indications for planned operative treatment of patients with a recurrent course of LTAI.

Adolescent↗

Role of the pancreas in the control of interdigestive gastrointestinal motility.

Our aim was to determine if the pancreas regulates the interdigestive motor patterns of the upper gut. Four dogs were prepared with gastric and intestinal manometry catheters and interdigestive (fasting) motility was measured before and after total surgical pancreatectomy. The characteristics of the gastric and intestinal migrating motor complex were very similar before and after pancreatectomy. The time intervals between successive migrating motor complexes in the antrum (145 +/- 11 vs. 135 +/- 15 min, mean +/- SE) or small intestine (133 + 10 vs. 137 +/- 16 min) were not significantly (p greater than 0.4) altered by pancreatectomy, but the antral motility index (the sum of the antral contractions in a 15-min period) was greater after pancreatectomy (53 +/- 6 vs. 27 +/- 4; p less than 0.05). Pancreatectomy led to undetectable plasma concentrations of pancreatic polypeptide, but had no effect on absolute concentrations of plasma motilin or on the cycling of plasma motilin in association with the duodenal migrating motor complex. We conclude that the pancreas and pancreatic polypeptide play little, if any, role in controlling canine interdigestive motility of the upper gut.

Animals↗