Dazopride

Dazopride, a substituted benzamide structurally related to metoclopramide, is a potent gastric prokinetic agent that prevents cisplatin-induced emesis in animals. Unlike metoclopramide, dazopride has no effect on dopamine receptors and therefore should not produce extrapyramidal side effects. In this dose-ranging trial, 23 patients with cancer receiving chemotherapy known to produce nausea and vomiting received three i.v. infusions of dazopride every 2 h beginning 30 min before the chemotherapy. Seven dose levels were explored ranging from 0.5 to 4.0 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, visual disturbances, and headaches. All side effects were transient and were not dose-related. Antiemetic effects were observed. Dazopride can be safely given on this schedule at doses of up to 4.0 mg/kg to patients receiving chemotherapy. On the basis of the results of this trial, further studies of this agent are warranted.

The gastric prokinetic and dopamine receptor antagonist activity of diazabicyclo[4.3.0], [4.4.0] (I, n = 1 or 2, R¹ and R² = H or Ph or R¹R² = double bond or ;CHCH:CHCH:) and oxa- and thia-azabicyclo[4.4.0] benzamides (II, R = H or Me and X = O, S or SO) related to the serotonin 5-HT₄ receptor agonist BRL 20627 is described.