TASK-1 inhibitors(Potassium channel subfamily K member 3 inhibitors), TASK-3 inhibitors(Potassium channel subfamily K member 9 inhibitors), Nitric oxide donors

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Hypoxia

Originator Organization

Galleon Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Galleon Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H30N2O2

InChIKeyXFDJYSQDBULQSI-QFIPXVFZSA-N

CAS Registry179915-79-8

Clinical Trials associated with (+)-Doxapram

NL-OMON37672 / CompletedNot Applicable

A Single Dose Study of the Pharmacodynamics, Tolerability, and Pharmacokinetics of GAL-054 - Single Dose PD and Tolerability of GAL-054

Start Date17 Oct 2011

Sponsor / Collaborator

Galleon Pharmaceuticals, Inc.

100 Clinical Results associated with (+)-Doxapram

100 Translational Medicine associated with (+)-Doxapram

100 Patents (Medical) associated with (+)-Doxapram

Literatures (Medical) associated with (+)-Doxapram

01 Oct 2021·Veterinary SurgeryQ2 · AGRICULTURAL & FORESTRY SCIENCE

Influence of doxapram and intermittent 10% carbon dioxide inspiration on cardiovascular and laryngeal functions in anesthetized dogs

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Reed, Rachel A. ; Sakai, Daniel M. ; Quandt, Jane E. ; Grimes, Janet A. ; Barletta, Michele ; Schmiedt, Chad W. ; Wallace, Mandy L. ; Howard, Shenise L.

AbstractObjectiveTo compare the effects of two doses of doxapram intravenous injection and carbon dioxide inhalation on the cardiovascular and laryngeal functions of anesthetized hounds.Study DesignExperimental study.AnimalsSix healthy adult dogs.MethodsIn a Latin‐square design, the mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously. The inspiratory normalized glottic gap areas (iNGGA) were measured before and after each stimulation with 0.55 mg/kg of doxapram (L‐DOX), 2.2 mg/kg of doxapram (H‐DOX), or 90 s of inhalation of 10% carbon dioxide in oxygen (I‐CO2). The stimulations were tested in duplicate or triplicate. Video clips of the laryngeal movement were scored by board‐certified surgeons masked to the treatment.ResultsThe MABP increased with L‐DOX and H‐DOX up to 81% (both p < .001 compared to I‐CO2), and persisted during the other stimulations (both p < .001). An intermittent tachycardic effect of up to 79% increase in HR was observed with doxapram. The HR following H‐DOX was higher than L‐DOX and I‐CO2 (both p < .016). Neither hypertension nor tachycardia was observed with I‐CO2. The iNGGA increased with all treatments (p < .001). The iNGGA was greater with H‐DOX than L‐DOX and I‐CO2 (both p < .007). All treatments received higher scores (all p < .001) with acceptable inter‐ and intra‐observers Krippendorff's alphas.ConclusionAll treatments were effective respiratory stimulants in anesthetized dogs; however, doxapram caused hypertension and tachycardia.Clinical SignificanceCarbon dioxide inhalation might improve arytenoid motion without cardiovascular effects in dogs during clinical airway examinations.

01 Feb 2020·Acta PhysiologicaQ2 · MEDICINE

Effects of the ventilatory stimulant, doxapram on human TASK‐3 (KCNK9, K2P9.1) channels and TASK‐1 (KCNK3, K2P3.1) channels

Q2 · MEDICINE

Article

Author: Veale, Emma L. ; MacIntyre, D. Euan ; Mathie, Alistair ; Cunningham, Kevin P.

AbstractAimsThe mode of action by which doxapram acts as a respiratory stimulant in humans is controversial. Studies in rodent models, have shown that doxapram is a more potent and selective inhibitor of TASK‐1 and TASK‐1/TASK‐3 heterodimer channels, than TASK‐3. Here we investigate the direct effect of doxapram and chirally separated, individual positive and negative enantiomers of the compound, on both human and mouse, homodimeric and heterodimeric variants of TASK‐1 and TASK‐3.MethodsWhole‐cell patch clamp electrophysiology on tsA201 cells was used to assess the potency of doxapram on cloned human or mouse TASK‐1, TASK‐3 and TASK‐2 channels. Mutations of amino acids in the pore‐lining region of TASK‐3 channels were introduced using site‐directed mutagenesis.ResultsDoxapram was an equipotent inhibitor of human TASK‐1 and TASK‐3 channels, compared with mouse channel variants, where it was more selective for TASK‐1 and heterodimers of TASK‐1 and TASK‐3. The effect of doxapram could be attenuated by either the removal of the C‐terminus of human TASK‐3 channels or mutations of particular hydrophobic residues in the pore‐lining region. These mutations, however, did not alter the effect of a known extracellular inhibitor of TASK‐3, zinc. The positive enantiomer of doxapram, GAL‐054, was a more potent antagonist of TASK channels, than doxapram, whereas the negative enantiomer, GAL‐053, had little inhibitory effect.ConclusionThese data show that in contrast to rodent channels, doxapram is a potent inhibitor of both TASK‐1 and TASK‐3 human channels, providing further understanding of the pharmacological profile of doxapram in humans and informing the development of new therapeutic agents.

01 Jan 2000·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Potentiation of Acetaminophen Hepatotoxicity by Doxapram in Mouse Primary Cultured Hepatocytes.

Q4 · MEDICINE

Article

Author: Takayanagi, Motoaki ; Kanno, Shuuichi ; Sasaki, Ken-Ichi ; Ishikawa, Masaaki ; Takayanagi, Yoshio

The augmentation by doxapram (DOP) of the reduction in viability and of the apoptosis of cells induced by acetaminophen (AA) was examined in mouse primary cultured hepatocytes. Loss of viability on exposure to AA and/or DOP in cultured hepatocytes was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the apoptosis of cultured hepatocytes was detected by nuclear morphologic observation and from a ladder-like DNA fragmentation pattern. The combination of AA (5 mM) and DOP (10, 20, 50 or 100 microM) potentiated the reduction in cell viability and increased the oxidative stress. Hepatocytes exposed for 24 h to AA (5 mM) plus DOP (100 microM), showed atrophy of nuclei, including chromatin condensation and a ladder-like DNA fragmentation pattern, characteristic of apoptosis. Benzyl-oxycarbonyl-Asp-CH2OC (O)-2,6-dichlorobenzene (Z-Asp-CH2-DCB, 50 microM), an inhibitor for caspases, improved the viability and ladder-like DNA fragmentation in cells exposed to DOP (200 or 500 microM) alone or AA ( 5 mM) plus DOP (100 microM). However, loss of viability on exposure to a high concentration of AA (10 mM) and ladder-like DNA fragmentation were not affected by Z-Asp-CH2-DCB. These results indicated that the synergistic increase in oxidative stress, activation of caspases and DNA fragmentation induced by DOP potentiated the hepatotoxicity of AA.

100 Deals associated with (+)-Doxapram

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hypoxia	Phase 1	-	Galleon Pharmaceuticals, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

(+)-Doxapram

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation