甲氧氯普胺致严重锥体外系反应、脱髓鞘脑病1例

目的：提示临床重视甲氧氯普胺引起的严重不良反应。方法：报道并分析甲氧氯普胺致严重锥体外系反应、脱髓鞘脑病1例。结果与结论：未见甲氧氯普胺致严重锥体外系反应、脱髓鞘脑病致死的报道。临床应高度重视甲氧氯普胺所致严重不良反应,应用时严格掌握剂量,注意个体差异。     

Anorexigenic effects of metoclopramide in rats

Metoclopramide has been found to decrease beef broth consumption in trained rats. This activity has been compared with that of the known anorexigenic agents, d-amphetamine and fenfluramine. These findings indicate that the drug exerts an anorexigenic effect in this species.     

Ceruletide vs. metoclopramide in postoperative intestinal paralysis

Sequential analysis of a double-blind clinical trial involving 26 patients demonstrated a statistically significant superiority of ceruletide over metroclopramide in restoring peristalsis in intestinal paralysis after abdominal surgery (P<0.05).     

Metoclopramide improves gastric motility in critically ill patients

Objective: To assess the effect of metoclopramide on gastric motility in critically ill patients. Design: Prospective, controlled, single-blind cross-over trial. Setting: A 10-bed general intensive care unit. Patients: Ten critically ill, enterally fed adult patients without renal failure. Interventions: Each patient received enteral feeding with Enrich via a nasogastric tube at 50 ml/h throughout the 5-h study period on two consecutive days. Either normal saline (control) or 10 mg of metoclopramide (treatment) was administered intravenously at the start of the study period in random order with cross-over design. Measurements and results: Gastric motility was measured indirectly by analysis of the absorption over time of 1.5 g of paracetamol administered into the stomach at the start of the study period together with a 100 ml bolus of Enrich feed. The rate of gastric emptying is proportional to the area under the line plot of serum paracetamol concentration against time over 120 min (AUC120). Eight of the ten patients studied showed an increased AUC120 with metoclopramide compared to that with saline. Statistical analysis with the Wilcoxon signed rank test gave a p value of 0.04, indicating a significant increase in gastric emptying following administration of metoclopramide. Conclusions: The administration of intravenous metoclopramide improved gastric emptying in a heterogeneous group of critically ill patients. Metoclopramide is a useful prokinetic drug in this patient population. Final revision received: 18 January 1999 Accepted: 2 March 1999     

The relative role of dopamine and norepinephrine receptor blockade in the action of antipsychotic drugs: Metoclopramide,thiethylperazine, and molindone as pharmacological tools

The aim of the present studies was to further delineate the role of striatal and limbic dopaminergic versus limbic noradrenergic blockade in the pharmacologic and perhaps therapeutic action of antipsychotic drugs. Metoclopramide shares many properties of antipsychotic neuroleptic drugs, including the production of extrapyramidal side effects, but is not an efficacious antipsychotic agent. This drug was a potent blocker of dopamine (DA) receptors in both striatum and limbic forebrain (comparable in potency to that of chlorpromazine) as evidenced from the increase in homovanillic acid in both brain structures. In contrast, metoclopramide was a weak inhibitor of the norepinephrine (NE) receptor-coupled adenylate cyclase system in the limbic forebrain. Molindone, which is reported not to block DA-sensitive adenylate cyclase, was a potent in vivo blocker of DA receptors in both striatum and limbic forebrain and also inhibited markedly the cyclic AMP response to NE in the limbic forebrain. The phenothiazine derivative, thiethylperazine, was also a potent blocker of DA receptors in both brain areas and displayed an IC₅₀ for NE blockade in the limbic forebrain comparable to that of chlorpromazine. The present results support the view that the ability and potency of drugs to block DA receptors parallels their ability and potency to cause extrapyramidal symptoms in man. Moreover, these results suggest that the blockade of NE receptor-coupled adenylate cyclase systems in brain may be relevant to both the pharmacologic and therapeutic activity of antipsychotic drugs.     

Relaxant effects of metoclopramide and magnesium sulfate on isolated pregnant myometrium: an in vitro study

BackgroundMetoclopramide and magnesium sulfate are extensively used agents in obstetrics. In this study, the relaxant properties of metoclopramide and magnesium sulfate on pregnant myometrium, together with the possible reversing influences of oxytocin and cabergoline (a dopamine D₂ receptor agonist), were investigated.MethodsMyometrial strips from 24 parturients were randomly allocated to four groups: control (Group CON), magnesium sulfate and oxytocin (Group MSO), metoclopramide and oxytocin (Group MEO), and metoclopramide and cabergoline (Group MEC). Myometrial strips were mounted on a myograph bathed in Krebs buffer. Saline (Group CON) and five incremental doses of magnesium sulfate (Group MSO) or metoclopramide (Groups MEO and MEC) were sequentially microinjected into the bath. Subsequently, oxytocin (Groups CON, MSO and MEO) or cabergoline (Group MEC) was microinjected into the bath. The myometrial contractile characteristics after each drug injection, including contractile force, interval and duration, were analyzed.ResultsMagnesium sulfate was more potent for prolonging myometrial contractile interval than reducing contractile force. Metoclopramide relaxed myometrial contractions by inhibiting contractile force and prolonging contractile interval in a concentration-dependent manner. Oxytocin reversed both the inhibited contractile force and the prolonged contractile interval caused by a high concentration of magnesium sulfate but accelerated the contractile interval and had no significant effect on the contractile force suppressed by metoclopramide. The relaxant effects of metoclopramide were completely reversed by cabergoline.ConclusionsBoth magnesium sulfate and metoclopramide relaxed myometrial contractions, and exhibited different responses to subsequent oxytocin treatment. The relaxant mechanism of metoclopramide may be via blockade of dopamine D₂ receptor, which requires further investigation.     

Controlling cancer chemotherapy-induced emesis An update

Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3–6 mg·kg^–1·d^–1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.     

Metoclopramide,domperidone and dopamine in man: actions and interactions

Summary The effects of oral doses of the dopamine antagonist antiemetics metoclopramide and domperidone on baseline and dopamine stimulated renal function and systemic haemodynamics were assessed in a placebo controlled crossover study in 9 healthy volunteers.Metoclopramide did not change baseline ERPF, GFR or FF over 2 h post dosing but it significantly reduced baseline U_NaV, U_KV, urine flow, urinary dopamine excretion, supine and erect diastolic blood pressure and supine systolic blood pressure. Domperidone and placebo did not cause these effects.Metoclopramide caused a marked rise and domperidone a small fall in plasma aldosterone concentration (PAC) but placebo was without effect. Neither antiemetic altered plasma renin activity (PRA) but a small fall occurred with placebo.Two hours after pretreatment with placebo dopamine (2 g/kg/min) increased effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium excretion rate (U_NaV), urine flow rate, urinary dopamine excretion rate, supine systolic blood pressure and supine and erect pulse rate and decreased the potassium excretion rate (U_KV), filtration fraction (FF) and supine diastolic blood pressure.Metoclopramide pretreatment, did not attenuate the dopamine induced rise in ERPF, GFR, urine flow, urinary dopamine excretion or supine systolic blood pressure but it did attenuate the rise in pulse rate, the fall in diastolic pressure, and the antikaliuretic effect of dopamine leading to a net kaliuresis when compared to placebo. Domperidone was similar to placebo.Neither metoclopramide nor domperidone given orally caused clinically important antagonism of the renal haemodynamic effects of dopamine. However the effects of metoclopramide on blood pressure and electrolyte excretion may have clinical importance.Metoclopramide has significant pharmacodynamic effects which are probably not due to DA₂ antagonism but may be mediated by DA₁ antagonism or be non-specific.Abbreviations DA dopamine - ERPF effective renal plasma flow - FF filtration fraction - GFR glomerular filtration rate - PAC plasma aldosterone concentration - PRA plasma renin activity - UV urine flow rate - U_NaV urinary sodium excretion rate (natriuresis) - U_KV urinary potassium excretion rate (kaliuresis) - HPLC high performance liquid chromatography.