Breathing Generation and Potential Pharmacotherapeutic Approaches to Central Respiratory Disorders

Abstract

Breathing is generated and controlled by a brainstem neuronal network. Both intrinsic and synaptic interactions are involved in respiratory rhythm generation and their contribution is state-dependent, changing with hypoxia and the neuromodulatory state. Cellular mechanisms involved in acute or chronic pathological conditions are still unknown. A dysfunction in the neuronal network that controls breathing may be involved in several respiratory disorders such as central sleep apnea, sudden infant death syndrome, congenital hypoventilation, and in some clinical conditions that produce breathing dysfunction such as drug-induced respiratory depression, obesity hypoventilation syndrome, etc. Despite the fact that several drugs are currently used to treat these diseases, the probable effects of this pharmacotherapy on the central rhythm generator and on other neuronal networks related with breathing control is poorly understood. Here, we review the current pharmacological approaches in the treatment of respiratory disorders, such as acetazolamide, theophylline, aminophylline, progesterone, nitric oxide. Possible effects of these drugs on the central respiratory network are discussed and putative therapeutic targets for the development of future pharmacological therapies suggested.

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

“…Our study confirmed the feasibility of automated cardiorespiratory measurements as biomarkers of treatment response (40). It also indicates that these breathing evaluations may be more reliable and valid than clinical instruments because parent questionnaire data were in disagreement with clinicians' observations.…”

Gasping Generation in Developing Swiss–Webster Mice In Vitro and In Vivo

“…However, alterations in the breathing-related modulation of hypoglossal motoneurons have been considered to be involved in sleep obstructive apnea [28][29][30]. Previous studies have shown that during specific experimental conditions, such as hypercapnia-hypoxia or lung inflation, the XII rhythmic activity might not be perfectly coupled to other respiratory motor outputs such as phrenic motoneurons [31,32].…”

Hypoxia Silences Retrotrapezoid Nucleus Respiratory Chemoreceptors via Alkalosis

“…Yet, we show here the first example of putative CRCs inhibited by hypocapnic hypoxia. The key evidence is that RTN photoinhibition no longer inhibited f R during hypoxia unless the plasma was reacidified with CO 2 or acetazolamide (Peña and García, 2006;Bell and Haouzi, 2010). Importantly, the difference between hypoxia and normoxia was Figure 12.…”

“…In reality, however, no CRC candidate (e.g., astrocytes, retrotrapezoid nucleus [RTN], serotonergic, orexinergic, and/or locus ceruleus neurons) has ever been shown to be inhibited by hypocapnic hypoxia. Hypocapnic hypoxia commonly produces sleep-disrupted breathing, a condition that improves with CO 2 supplementation or acetazolamide administration (Peña and García, 2006;Bell and Haouzi, 2010;Ainslie et al, 2013;Javaheri and Dempsey, 2013).…”