motilin and Vomiting

Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.. Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?. Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use.. Vomiting: Rationale for 5-HT. Several drug classes inhibiting vomiting have no scientific rationale. NK

Topics: Gastric Emptying; Gastroparesis; Humans; Motilin; Nausea; Serotonin; Vomiting

Gastroparesis is a symptomatic chronic disorder characterized by delayed gastric emptying without a mechanical obstruction. Gastroparesis is most often associated with diabetes, gastric surgery, and systemic disorders affecting the neuromuscular control of the stomach. However, no underlying etiology can be found in up to 40% of patients, a condition referred to as idiopathic gastroparesis. Due to the numerous potential etiologies and the highly variable clinical manifestations, the management of gastroparesis is particularly challenging. The purpose of this review is to provide an update on the use of antiemetics, prokinetics, and tricyclics for the treatment for nausea and vomiting associated with gastroparesis.

Topics: Antidepressive Agents, Tricyclic; Antiemetics; Dopamine Antagonists; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Motilin; Nausea; Vomiting

Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.

Topics: Animals; Antiemetics; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Erythromycin; Female; Gastric Mucosa; Gastrointestinal Agents; Gastrointestinal Motility; Male; Motilin; Muscle Contraction; Nicotine; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Shrews; Stomach; Vagus Nerve; Vomiting

Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

Topics: Analgesics; Animals; Calcitonin; Calcium; Dogs; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Motilin; Muscle Contraction; Parasympathetic Nervous System; Stomach; Synaptic Transmission; Transducers, Pressure; Vagotomy; Vomiting

The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide. In the fasting state, EM-523 given i.v. or i.d. at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine. The pattern of the contractions was very similar to that induced by motilin. In the digestive state, EM-523 increased the amplitude of gastric contractions. Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523. Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state. The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action. These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth.

Topics: Animals; Atropine; Dogs; Erythromycin; Fasting; Gastrointestinal Motility; Male; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Vomiting

The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine. Cisplatin given intravenously in a dose of 2 mg/kg resulted in complete interruption of IDMA and produced predominantly phase II-like activity, lasting as long as 24 hr. Six of the seven dogs exhibited retropropagation of spike bursts from the jejunum to the antrum which was accompanied by emesis. Retropropagation of spike bursts did not occur in one dog who did not exhibit emesis. In addition, abnormal spike bursts occurred frequently, including simultaneously occurring spike bursts in both duodenum and jejunum and nonpropagating short spike bursts in isolated segments of the upper small intestine. As phase III of IDMA disappeared, plasma motilin concentrations remained comparable to those in phase II of normal IDMA but without the cyclic increases. These studies indicate that cisplatin interrupts the regular cycle of IDMA as well as the plasma motilin cycle and produces retropropagation of spike bursts and abnormal spike bursts. These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs.

Topics: Animals; Behavior, Animal; Cisplatin; Dogs; Electrophysiology; Infusions, Intravenous; Intestine, Small; Motilin; Periodicity; Stomach; Vomiting

Topics: Animals; Dogs; Erythromycin; Gastrointestinal Motility; Humans; Motilin; Vomiting