Disease relevance of doxapram

• Prolonged doxapram infusion in obesity-hypoventilation syndrome [1].
• Hyperventilation induced by 30 minutes of exercise, placement in a 39 degrees C water bath, or intravenous doxapram increased venous blood pH in dog 1 and control dogs, but transient hemoglobinemia, hemoglobinuria, and severe bilirubinuria occurred only in the studied patient [2].
• OBJECTIVE: Doxapram, routinely used in premature infants treated for apnea of prematurity unresponsive to methylxanthines, has been related to cardiac conduction disorders [3].
• Intravenous doxapram increased ventilation but did not reverse respiratory failure [4].
• Neither the cognitive intervention nor doxapram-induced hyperventilation produced significant changes in V(t) irregularity [5].

Psychiatry related information on doxapram

• METHOD: Quantitative water method positron emission tomography was used to obtain brain images of five untreated subjects with panic disorder and five healthy comparison subjects before and during anxiogenic challenge with intravenous doxapram, an acute respiratory stimulant [6].
• METHODS: The effects of doxapram were determined for cue and contextual fear conditioning, the open field test, and the social interaction test [7].
• Respiratory psychophysiology and anxiety: cognitive intervention in the doxapram model of panic [8].
• When administered during an episode of spontaneous FB during REM sleep, both caffeine and doxapram caused stimulation of the frequency and depth of breathing [9].
• Four cases are reported where patients reacted with severe restlessness, violence or hallucinations at low doses of doxapram infusion [10].

High impact information on doxapram

• RESULTS: Baseline perfusion of the orbitofrontal cortex predicted panic attacks: lower perfusion was associated with heightened anxiety in response to doxapram challenge [6].
• Doxapram, by inducing hyperventilation, may be a useful adjunct to existing animal anxiety models for improving validity for panic anxiety [7].
• The effect of doxapram may result from activation of neurons in the amygdala [7].
• METHODS: Forty infants (mean +/- SEM, 28.9 +/- 0.3 weeks of gestation) who were given intravenous doxapram, 0.5 to 1 mg/kg per hour, at 15.9 +/- 2.4 days of life were evaluated prospectively [3].
• The biotransformation of doxapram, a respiratory stimulant was studied with use of explants from human fetal livers (n = 15 fetuses) obtained from therapeutic abortions (gestational age, 10 to 20 weeks) [11].

Chemical compound and disease context of doxapram

• Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study [12].
• A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity [13].
• Four patients (ages 43 to 51) with primary alveolar hypoventilation (PAH) syndrome were studied to characterize the pharmacologic augmentation of ventilation with intravenous doxapram hydrochloride [14].
• CONCLUSION: Doxapram substantially reduced the frequency of apnoea, bradycardia and hypoxaemia in these patients with caffeine-resistant apnoea of prematurity [15].
• BACKGROUND: Doxapram is used to treat apnea of prematurity when there is an insufficient response to methylxanthine treatment [16].

Biological context of doxapram

• Neither aspirin nor doxapram affect the shape of this stimulus-response curve, and in particular do not prevent low FIO2 associated inhibition of hypoxic pulmonary vasoconstriction [17].
• Six hours after starting doxapram, mean arterial blood pressure was significantly elevated, and continued to increase during the 24 hours of therapy [18].
• Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001) [19].
• Doxapram therapy was associated with significant increases in minute ventilation, tidal volume, mean inspiratory flow, and airway pressure 100 msec after occlusion [18].
• We were able to monitor intracranial pressure (ICP) throughout the course of doxapram via an ICP monitor [20].

Anatomical context of doxapram

• Doxapram induced c-Fos-like immunoreactivity in the central nucleus of the amygdala but not the lateral nucleus or the nucleus tractus solitarius [7].
• OBJECTIVE: The aim was to characterise stimulus-response curves for hypoxic pulmonary vasoconstriction and to observe the effects of drugs reputed to enhance it: aspirin (a cyclo-oxygenase inhibitor), and doxapram (a peripheral chemoreceptor agonist) [17].
• METHODS: Mean pulmonary artery pressure (Ppa) versus fraction of inspired O2 (FIO2) relationships were studied in 18 intact anaesthetised piglets, before and after the intravenous administration, in random order, of either physiological saline, 1 g aspirin, or 20 mg.kg-1 doxapram [17].
• Potencies of doxapram and hypoxia in stimulating carotid-body chemoreceptors and ventilation in anesthetized cats [21].
• Doxapram also increased phrenic-nerve activity in doses as low as 0.2 mg/kg, iv [21].

Associations of doxapram with other chemical compounds

• Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report [22].
• In a double-blind study of 100 outpatients receiving an anaesthetic sequence of methohexitone, nitrous oxide and halothane, significant shortening of recovery time was produced by the i.v. administration of doxapram hydrochloride at the end of anaesthesia [23].
• The results confirm the absence of side-effects of doxapram as compared to caffeine when used as respiratory stimulant, especially in neonates [24].
• 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 [25].
• We measured resting VE and blood gas tensions and pH and ventilatory responses (VR) to NaCN, dopamine and Doxapram in awake goats before and after UCBE [26].

Gene context of doxapram

• Chimera studies suggested that the carboxy terminus of TASK-1 is important for doxapram inhibition [27].
• Doxapram stimulates ventilation through an effect on carotid bodies, and we hypothesized that stimulation might result from inhibition of TASK-1 or TASK-3 K channel function [27].
• The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure [28].
• The oxidative pathway producing keto-doxapram, or AHR 5955 and AHR 5904, is more active than the de-ethylation producing the analog of doxapram AHR 0914 [11].
• Doxapram increases corticotropin-releasing factor immunoreactivity and mRNA expression in the rat central nucleus of the amygdala [29].

Analytical, diagnostic and therapeutic context of doxapram

• The concentrations of doxapram and its metabolites (AHR 0914, an analog of doxapram, AHR 5955 or ketodoxapram, and AHR 5904) were measured by high pressure liquid chromatography [11].
• Doxapram metabolism in human fetal hepatic organ culture [11].
• CONCLUSIONS: Doxapram enhanced anxiety-related behaviors in four animal models of anxiety that involve conditioning or spontaneous avoidance [7].
• We treated a brain-damaged 8-month-old male with iv doxapram in order to discontinue mechanical ventilation [20].
• After denervation of the peripheral chemoreceptors, doxapram in doses as large as 6 mg/kg failed to stimulate ventilation [21].

References