Identification and Characterization of GAL-021 as a Novel Breathing Control Modulator

Anesthesiology
Francis J GolderD Euan MacIntyre

Abstract

The authors describe the preclinical pharmacological properties of GAL-021, a novel peripheral chemoreceptor modulator. The ventilatory effects of GAL-021 were characterized using tracheal pneumotachometry (n = 4 to 6), plethysmography (n = 5 to 6), arterial blood gas analyses (n = 6 to 11), and nasal capnography (n = 3 to 4) in naive animals and those subjected to morphine-induced respiratory depression. Morphine analgesia in rats was evaluated by tail-flick test (n = 6). Carotid body involvement in GAL-021 ventilatory effects was assessed by comparing responses in intact and carotid sinus nerve-transected rats. Hemodynamic effects of GAL-021 were evaluated in urethane-anesthetized rats (n = 7). The pharmacological profile of GAL-021 in vitro was investigated using radioligand binding, enzyme inhibition, and cellular electrophysiology assays. GAL-021 given intravenously stimulated ventilation and/or attenuated opiate-induced respiratory depression in rats, mice, and nonhuman primates, without decreasing morphine analgesia in rats. GAL-021 did not alter mean arterial pressure but produced a modest increase in heart rate. Ventilatory stimulation in rats was attenuated by carotid sinus nerve transection. GAL-021 inhibited KCa1.1 ...Continue Reading

References

Jan 1, 1978·Respiration Physiology·M A Epstein, R A Epstein
Apr 1, 1981·Canadian Journal of Physiology and Pharmacology·G E Bisgard
Nov 1, 1984·Anesthesiology·D S SchulmanS I Rapoport
Jun 14, 2000·Journal of Applied Physiology·N R Prabhakar
Oct 7, 2003·The Journal of Physiology·Henri J L M TimmersJacques W M Lenders
Apr 6, 2004·Methods in Enzymology·Keith Buckler, Eric Honoré
Jun 9, 2004·The Journal of Biological Chemistry·Andrea L MeredithRichard W Aldrich
Jan 18, 2007·CNS Drug Reviews·C Spencer Yost
Feb 29, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francis J GolderGordon S Mitchell
May 12, 2009·The AAPS Journal·Jane V Aldrich, Jay P McLaughlin
Jun 19, 2009·Advances in Experimental Medicine and Biology·Prem Kumar
Dec 17, 2009·Anesthesiology·Albert DahanTerry W Smith
Aug 26, 2010·Respiratory Physiology & Neurobiology·Chris PeersA Mark Evans
Mar 8, 2011·Archives of Disease in Childhood·Barbara SchmidtUNKNOWN Steering Committee of the Caffeine for Apnea of Prematurity (CAP) trial
Jan 1, 2010·Journal of Asthma and Allergy·Xiaojia WangMichael R Van Scott
May 23, 2012·The Journal of Physiology·Souren MkrtchianLars I Eriksson
Jun 21, 2013·The New England Journal of Medicine·Stavros G MemtsoudisMadhu Mazumdar
Oct 25, 2014·F1000prime Reports·Rutger van der SchierMarieke Niesters
Oct 28, 2014·Frontiers in Physiology·Bo H BentzenMorten Grunnet

❮ Previous
Next ❯

Citations

Mar 20, 2018·Anesthesiology·Albert DahanMarieke Niesters
Jul 13, 2021·Frontiers in Pharmacology·Santhosh BabyStephen Lewis
Jul 2, 2019·Journal of Medicinal Chemistry·Mauricio BedoyaDavid Ramírez

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.