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The American Review of Respiratory... Dec 1985Almitrine, a peripheral chemoreceptor agonist, exerts beneficial effects on blood gases in patients with hypoxic chronic air-flow obstruction, but as these patients... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Almitrine, a peripheral chemoreceptor agonist, exerts beneficial effects on blood gases in patients with hypoxic chronic air-flow obstruction, but as these patients exhibit poor ventilatory responses to hypoxia, the mechanism for this improvement is not clear. The effect of a 100-mg dose of almitrine given orally on ventilation and the steady-state hypoxic ventilatory response (HVR) were measured in a randomized, double-blind, placebo-controlled manner in 7 patients with severe hypoxic chronic air-flow obstruction. The isocapnic HVR (delta VE/delta SaO2) was calculated from the changes in ventilation and SaO2 from breathing 60% O2 to breathing air with the addition of CO2 to maintain isocapnia (as estimated from a transcutaneous CO2 electrode). Resting ventilation while breathing air and isocapnic HVR were measured before and 3 h after almitrine or placebo. Almitrine caused no significant change in resting ventilation. There was, however, a large increase in HVR after almitrine (almitrine: -1.5 L/min/%SaO2; range, -0.5 to -3.1; control: -0.4; range, -0.3 to -1.3), but no change after placebo. Almitrine is a powerful stimulant of chemosensitivity and of the hypoxic ventilatory response in chronic hypoxemia, with potential benefit to patients with chronic air-flow obstruction in respiratory failure.
Topics: Aged; Almitrine; Blood Gas Analysis; Carbon Dioxide; Central Nervous System Stimulants; Double-Blind Method; Humans; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Piperazines; Plethysmography; Random Allocation; Respiration
PubMed: 2866741
DOI: 10.1164/arrd.1985.132.6.1233 -
Respiratory Research Jan 2023Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously...
BACKGROUND
Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined.
METHODS
We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO/FiO ratio < 100 with FiO > 80% after a single awake prone positioning session. Patients with an increase in PaO/FiO ratio > 20% were considered as responders.
RESULTS
Overall, almitrine increased the PaO/FiO ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders.
CONCLUSIONS
Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.
Topics: Humans; Male; Middle Aged; Aged; Almitrine; COVID-19; Cannula; Respiratory Distress Syndrome; Hypoxia; Oxygen
PubMed: 36600234
DOI: 10.1186/s12931-022-02308-y -
Lancet (London, England) Oct 1985
Clinical Trial
Topics: Aged; Almitrine; Central Nervous System Stimulants; Humans; Lung Diseases, Obstructive; Middle Aged; Peripheral Nervous System Diseases; Piperazines; Respiratory Insufficiency
PubMed: 2864548
DOI: 10.1016/s0140-6736(85)90814-1 -
Chest Nov 2020
Topics: Aged; Almitrine; Betacoronavirus; Blood Gas Analysis; COVID-19; Coronavirus Infections; Extracorporeal Membrane Oxygenation; Female; Humans; Hypoxia; Male; Middle Aged; Oxygen; Oxygen Inhalation Therapy; Pandemics; Partial Pressure; Patient Positioning; Pneumonia, Viral; Positive-Pressure Respiration; Prone Position; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; SARS-CoV-2; Treatment Outcome
PubMed: 32512007
DOI: 10.1016/j.chest.2020.05.573 -
The American Review of Respiratory... May 1992Almitrine and doxapram, two structurally unrelated peripheral chemoreceptor agonists, have been shown to enhance hypoxic pulmonary vasoconstriction in anesthetized dogs.... (Comparative Study)
Comparative Study
Almitrine and doxapram, two structurally unrelated peripheral chemoreceptor agonists, have been shown to enhance hypoxic pulmonary vasoconstriction in anesthetized dogs. We hypothesized that these drugs would increase pulmonary vascular tone and improve gas exchange in canine lung injury caused by oleic acid (OA). Pulmonary hemodynamics and gas exchange were investigated in pentobarbital-anesthetized dogs before and after intravenously administered OA 0.09 ml/kg and again after placebo (n = 6), almitrine 2 micrograms/kg/min (n = 6), or doxapram 20 micrograms/kg/min (n = 6) in a randomized order. Cardiac output (Q) was manipulated using a femoral arteriovenous bypass and an inferior vena cava balloon catheter to construct mean pulmonary artery pressure (Ppa)-Q plots in order to discriminate active from passive changes in Ppa. Gas exchange was assessed by measuring arterial PO2 and intrapulmonary shunt, determined using a sulfur hexafluoride infusion. OA increased Ppa over the range of Q studied, and it deteriorated gas exchange by an increase in intrapulmonary shunt. After OA, placebo had no effect on Ppa, arterial PO2, or intrapulmonary shunt. Both almitrine and doxapram further increased Ppa at all levels of Q studied, but they did not affect indices of gas exchange after OA. We conclude that in this experimental model of acute lung injury, almitrine and doxapram induce pulmonary vasoconstriction without, however, diverting blood flow toward better oxygenated lung regions.
Topics: Almitrine; Animals; Dogs; Doxapram; Oleic Acid; Oleic Acids; Pulmonary Circulation; Pulmonary Edema; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Vasoconstriction
PubMed: 1586044
DOI: 10.1164/ajrccm/145.5.1042 -
Anaesthesia, Critical Care & Pain... Aug 2020
Topics: Almitrine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Nitric Oxide; Oxygen Consumption; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; SARS-CoV-2; Vasoconstrictor Agents
PubMed: 32505755
DOI: 10.1016/j.accpm.2020.05.014 -
Bulletin Europeen de Physiopathologie... 1984
Topics: Almitrine; Animals; Biomechanical Phenomena; Carotid Body; Chronic Disease; Dogs; Humans; Hypoxia; Lung Diseases, Obstructive; Piperazines; Respiration; Respiratory Insufficiency
PubMed: 6722367
DOI: No ID Found -
PloS One 2023Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital,...
Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice.
Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.
Topics: Animals; Mice; Toxoplasma; Almitrine; Drug Repositioning; COVID-19; Toxoplasmosis; Malaria
PubMed: 37418497
DOI: 10.1371/journal.pone.0288335 -
Revista de Igiena, Bacteriologie,... 1989
Review
Topics: Almitrine; Chemoreceptor Cells; Humans; Respiration; Respiratory System; Respiratory Tract Diseases
PubMed: 2555895
DOI: No ID Found -
La Revue de Medecine Interne 1985
Review
Topics: Almitrine; Animals; Blood Pressure; Blood Vessels; Chemoreceptor Cells; Dogs; Hemodynamics; Humans; Lung; Lung Diseases, Obstructive; Piperazines; Pulmonary Circulation; Pulmonary Gas Exchange; Respiration; Vasodilator Agents
PubMed: 3914681
DOI: 10.1016/s0248-8663(85)80138-7