Doxapram

Doxapram is a respiratory stimulant. Doxapram increases breathing rate and depth by acting on the brain's respiratory centers and peripheral chemoreceptors. Doxapram inhibits TASK-1, TASK-3, TASK-1/TASK-3 heterodimeric channel function with EC₅₀s of 410 nM, 37 μM, 9 μM, respectively. Doxapram inhibits the Ca²⁺-activated potassium current (IC₅₀ ≈ 13 μM) and Ca²⁺-independent potassium current (IC₅₀ ≈ 20 μM) in type I cells of the carotid body. Doxapram significantly prolongs the effective refractory period of the atrium and has an anti-arrhythmic effect. Doxapram can be used for the study of respiratory depression such as post-anesthesia respiratory depression, chronic obstructive pulmonary disease and apnea of prematurity^{[1][2][3][4][5][6]}. In Vitro:Doxapram (0.01-100 μM, 10-30 min) inhibits human and porcine TASK-1 with IC₅₀s of 0.88 and 0.93 μM in human and porcine atrial muscle cells^[6].
In Vivo:Doxapram (0.05-0.25 mg/kg, i.v.) selectively but indirectly activate medullary respiratory neurons through carotid and aortic chemoreceptor stimulation in cats^[4].
Doxapram (> 1 mg/kg, i.v.) stimulates the brainstem respiratory center rather than the peripheral chemoreceptors in dogs^[4].
Doxapram (1-2 mg/kg, i.v., single dose or once daily for 14 days) has a specific anti-arrhythmic effect on the atrium in domestic pigs^[6].