The Ventilatory Effects of Doxapram in Normal Man

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO₂ production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level.

2. Doxapram changed neither resting oxygen uptake nor CO₂ production but produced a substantial increase in resting ventilation at both levels of end-tidal CO₂ studied.

3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min⁻¹ (%Sao₂)⁻¹ to −1.63 ± 0.9 litres min⁻¹ (%Sao₂)⁻¹. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO₂ by 0.5 kPa without adding doxapram.

4. The slope of the ventilatory response to rebreathing CO₂ rose from 11.6 ± 5.3 litres min⁻¹ kPa⁻¹ to 20,4 ± 9.8 litres min⁻¹ kPa⁻¹ during doxapram infusion.

5. The marked increase in the ventilatory response to CO₂ implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.