Respiratory stimulation by almitrine during acute or chronic hypoxia/hypercapnia in rats

In anaesthetized rats studied in a body plethysmograph, 1-(4'6-diallylamino-2'-triazinyl)-4(bis parafluorobenzydryl) piperazine (almitrine) caused large increases in ventilation (VE) which were abolished by cutting the IXth and Xth cranial nerves. Maximal effects followed infusions of 0.5-1 mg X kg-1; the solvent had no action. When the rats breathed 10% O2 or 10% O2 + 5% CO2, gas mixtures which increased VE, almitrine caused further increases in VE and improved blood gas tensions. Chronically hypoxic (4 weeks in 10% O2) and chronically hypoxic and hypercapnic rats (4 weeks in 10% O2 + 4% CO2), kept in an environmental chamber, were similarly studied. While they breathed, under anaesthesia, the gas mixture to which they had been chronically exposed, infusions of almitrine caused further large increases in VE and improved blood gas tensions. Thus almitrine stimulates VE, probably through peripheral chemoreceptors, when these are already strongly stimulated. This drug increased both tidal volume and frequency and thus increased alveolar ventilation. No convulsant action was observed. It caused a fall in blood pressure which lasted 5-10 min and was seen with urethane but not pentobarbitone anaesthesia; it was not due to the solvent.