Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted. Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels. Used as temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.

Doxapram is racemic and exists as a racemate with positive ( ) and negative (−) enantiomers. The respiratory stimulant properties of doxapram would be stereoselective and could be evaluated by chirally separating doxapram into its ( ) enantiomer (GAL-054) and (−) enantiomer (GAL-053). Pre-clinically we demonstrated that the ( ) enantiomer, GAL-054, and not the (−) enantiomer, GAL-053, dose-dependently increased minute volume when administered intravenously to drug naïve and opioid challenged rats and cynomolgus monkeys. Moreover, the deleterious side-effects of agitation and seizures were restricted to GAL-053. There were minimal behavioral changes observed in rats and monkeys receiving GAL-054. Thus, GAL-054 is the eutomer and GAL-053 the distomer of doxapram. Unfortunately, in conscious rats GAL-054 increased blood pressure approximately 15–20% above baseline values at doses that were moderately respiratory stimulant. This effect was confirmed in a Phase 1 clinical trial evaluating the effects of GAL-054 in healthy volunteers (Galleon Pharmaceuticals, unpublished data). Thus, the ventilatory stimulant and pressor effects of doxapram cannot be separated by enantiomeric separation of the racemate.

Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted. Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels. Used as temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.

Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted. Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels. Used as temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.

Doxapram is racemic and exists as a racemate with positive ( ) and negative (−) enantiomers. The respiratory stimulant properties of doxapram would be stereoselective and could be evaluated by chirally separating doxapram into its ( ) enantiomer (GAL-054) and (−) enantiomer (GAL-053). Pre-clinically we demonstrated that the ( ) enantiomer, GAL-054, and not the (−) enantiomer, GAL-053, dose-dependently increased minute volume when administered intravenously to drug naïve and opioid challenged rats and cynomolgus monkeys. Moreover, the deleterious side-effects of agitation and seizures were restricted to GAL-053. There were minimal behavioral changes observed in rats and monkeys receiving GAL-054. Thus, GAL-054 is the eutomer and GAL-053 the distomer of doxapram. Unfortunately, in conscious rats GAL-054 increased blood pressure approximately 15–20% above baseline values at doses that were moderately respiratory stimulant. This effect was confirmed in a Phase 1 clinical trial evaluating the effects of GAL-054 in healthy volunteers (Galleon Pharmaceuticals, unpublished data). Thus, the ventilatory stimulant and pressor effects of doxapram cannot be separated by enantiomeric separation of the racemate.