Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown in both mice and rats that the LD50 value for doxapram is reduced in rodents treated with narcotic analgesics. In both species the site of the toxic interaction appears to be the cardiovascular system. Doxapram alone, in sub-lethal doses, appears to cause conduction defects in the heart and this action of doxapram is increased in rodents treated with morphine. The enhancement of the toxicity of doxapram by morphine appears to involve an action in the central nervous system probably not related to respiratory depression.
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PMID:A study of the enhanced toxicity of doxapram in rodents treated with narcotic analgesics. 2 62

The effectiveness of naloxone and doxapram in reversing the respiratory depressant actions of fentanyl and droperidol in the rabbit has been examined. Both drugs did not reverse fully the depression of respiratory frequency produced by the neuroleptanalgesic agents. Doxapram also failed to reverse fully the depression of minute volume produced by fentanyl and droperidol, although naloxone was adequate in this respect. However, analysis of arterialized venous blood showed that both naloxone and doxapram not only prevented the increase in PCO2 caused by fentanyl and droperidol, but caused also a significant decrease. A reduction in PCO2 was seen also when either naloxone or doxapram was given to untreated rabbits. With doxapram this appeared to be a result of pure respiratory stimulation. Naloxone also produced a reduction in standard bicarbonate.
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PMID:A study of naloxone and doxapram as agents for the reversal of neuroleptanalgesic respiratory depression in the conscious rabbit. 3 Apr 67

Doxapram administered as a single injection or infusion satisfactorily counteracted the respiratory depression produced by buprenorphrine when administered one hour after the analgesic in healthy subjects. The respiratory stimulant effect was relatively short lived, however, a more prolonged effect was found by study of the displacement of the carbon dioxide response curve.
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PMID:The effect of doxapram on buprenorphine induced respiratory depression. 33 48

A 2X2 factorially designed study has been done to determine the respiratory effects of pentazocine and doxapram in terms of the minute ventilation end-expiratory PCO2 response curve. Pentazocine 30 mg intramuscularly produced marked respiratory depression. Doxapram 60 mg intramuscularly produced significant respiratory stimulation. When this dose of doxapram was given in combination with 30 mg pentazocine it produced significant reduction in the amount of respiratory depression induced by the narcotic. The statistical analysis did not show that there was anything to suggest this effect was more than additive.
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PMID:[The respiratory effect of doxapram and pentazocine and their interaction (author's transl)]. 121 84

Doxapram, 0.05 mg/kg bodyweight/min, was infused during the second hour of 2 h halothane anaesthesia in six ponies. Two of the ponies were anaesthetised on a second occasion as controls and given 5 per cent dextrose in place of the doxapram. Respiratory depression typical of halothane anaesthesia in ponies developed in the first hour of anaesthesia and continued during the second hour in the control animals. During doxapram infusion arterial carbon dioxide tension decreased and pH increased. Arterial blood pressure increased but there was no change in pulse rate, the electrocardiogram or arterial oxygen tension. Anaesthesia lightened during doxapram infusion necessitating an increase in the vapouriser setting in order to prevent arousal. Recovery from anaesthesia appeared unaffected by the doxapram infusion.
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PMID:Doxapram infusion during halothane anaesthesia in ponies. 212 75

Doxapram was administered to 50 spontaneously breathing patients receiving enflurane and nitrous oxide for surgical anesthesia. A similar group acted as control. Significant depression of ventilation did not occur in the control group of patients, nor did doxapram produce a reduction of end tidal CO2 concentrations. It is suggested that surgical stimulation and concomitant nitrous oxide administration reduced the ventilatory depressant effect of enflurane and that the effect of doxapram was attenuated by the actions of enflurane on the peripheral chemoreceptors.
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PMID:No effect of doxapram during enflurane-nitrous oxide anesthesia. 212 61

A double-blind crossover volunteer trial has been carried out to determine if oral doxapram reduces the respiratory depression caused by morphine 0.12 mg kg-1 i.m. Doxapram was given to the subjects 90 min before the morphine and significantly reduced the displacement of the ventilatory response to carbon dioxide caused by the morphine. This occurred despite the fact that the plasma concentrations of doxapram were significantly lower when the subject had been given morphine than when a placebo injection had been administered. Doxapram alone in doses of 300 mg and 600 mg did not alter significantly the respiratory variables measured in this study.
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PMID:Effect of oral doxapram on morphine-induced changes in the ventilatory response to carbon dioxide. 249

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.
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PMID:Doxapram and the neuromuscular junction. 231 31

The effectiveness of 4-aminopyridine, doxapram, or yohimbine as antagonists against xylazine-induced CNS depression in dogs was evaluated and compared, using the 2-way shuttle-avoidance paradigm. All drugs were given IV to 5 male dogs trained to avoid mild shock by jumping over a hurdle within 10 s after initiation of an audible tone. At dosages of 1 and 2 mg/kg of body weight, xylazine abolished or significantly decreased the mean number of avoidance responses and significantly increased the mean latency of avoidance responses. The analeptic 4-aminopyridine (0.5 mg/kg) did not significantly antagonize xylazine in all dogs. One dog convulsed both times it was given xylazine followed by 4-aminopyridine, but did not convulse when given either drug alone. Doxapram (5.5 mg/kg), a short-acting analeptic and respiratory stimulant, was only partially effective in antagonizing xylazine, and its antagonistic actions were brief. Yohimbine (0.1 mg/kg), an alpha 2-adrenoreceptor-blocking agent, was superior to 4-aminopyridine and doxapram in its ability to antagonize xylazine-induced CNS depression. Yohimbine consistently increased the mean number of avoidance responses to the maximum of 8 and consistently decreased the mean latency of avoidance responses to control values in dogs given 1 or 2 mg of xylazine/kg. In dogs given 2 mg of xylazine/kg, yohimbine was significantly more effective than 4-aminopyridine or doxapram in its ability to increase the mean number of avoidance responses and decrease the mean latency of avoidance responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of xylazine-induced depression of shuttle-avoidance responses in dogs by administration of 4-aminopyridine, doxapram, or yohimbine. 287 3

Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH.
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PMID:Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia. 289 65


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