Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep

Grace, Kevin P.; Hughes, Stuart W.; Horner, Richard L.

doi:10.1164/rccm.201209-1654oc

Cited by 173 publications

(166 citation statements)

References 39 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…The latter point is significant because the major neurotransmitters involved in modulating pharyngeal muscle tone across sleep-wake states 40, 48 are also involved in sleep-wake regulation and other components of cognition, mood, as well as brain and autonomic functions (e.g., 49 ) such that some off-target effects are likely.…”

Section: Strategic Directions From the Phenotype Model And Identifmentioning

confidence: 99%

“…If this effect can be achieved then the potential of therapeutic efficacy is realistic. Manipulation of certain potassium channels at the hypoglossal motor pool can activate the tongue musculature throughout sleep to waking levels 40, 42 . Importantly, it has been recently shown that introducing a “designer” receptor into the hypoglossal motor pool, and selectively modulating it with a “designer” drug, led to significant and sustained increases in tongue muscle activity and increases in upper airway size in pre-clinical rodent models 60, 61 .…”

Section: Mapping Potential Drug Targets In the Circuitry Controllimentioning

confidence: 99%

“…Desipramine is a tricyclic anti-depressant with strong noradrenergic and some anti-muscarinic effects. It was selected for those studies with the aim of preserving the excitatory noradrenergic tone to the pharyngeal motor pools that is normally withdrawn in sleep 39, 62 , and to counter the strong muscarinic cholinergic receptor-mediated inhibition of the tongue musculature that occurs in REM sleep 40 .…”

Section: Mapping Potential Drug Targets In the Circuitry Controllimentioning

confidence: 99%

See 2 more Smart Citations

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

2017

Self Cite

View full text Add to dashboard Cite

There is currently no pharmacotherapy for OSA, but there is no principled a-priori reason why there shouldn’t be one. This review identifies a rational decision-making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a-priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any OSA pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for OSA pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for OSA treatment that are of most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to OSA pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of “druggable” targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure OSA per se, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.

show abstract

Section: Strategic Directions From the Phenotype Model And Identifmentioning

confidence: 99%

Section: Mapping Potential Drug Targets In the Circuitry Controllimentioning

confidence: 99%

Section: Mapping Potential Drug Targets In the Circuitry Controllimentioning

confidence: 99%

See 1 more Smart Citation

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…6) localização dos músculos diafragma, genioglosso e transverso do abdômen para inserção de eletrodos de registro (GRACE et al, 2013;HUCKSTEPP et al, 2015;JANCZEWSKI et al, 2013;MORAES et al, 2013) Após a finalização dos procedimentos cirúrgicos, o anestésico halotano foi substituído pelo anestésico endovenoso uretano (1,2 g/kg). …”

Section: Procedimentos Cirúrgicosunclassified

“…A musculatura da laringe esta envolvida em diversas funções fisiológicas como o funcionamento adequado das cordas vocais, na regulação da abertura da glote, no controle da resistência das vias aéreas e em reflexos protetores das vias aéreas (DUTSCHMANN; DICK, 2012;DUTSCHMANN et al, 2014;HORNER, 2013). Os nossos resultados apresentam evidências de que a estimulação do pFRG/RTN foi capaz de promover um aumento da atividade respiratória do músculo genioglosso.…”

Section: Envolvimento Do Núcleo Retrotrapezoide Na Fase Pré -Inspiratunclassified

Interação entre o grupamento parafacial/núcleo retrotrapezóide e a região de kölliker-fuse na modulação do padrão respiratório.

Lucena¹

View full text Add to dashboard Cite

An unusual presentation of severe obstructive sleep apnea with nocturnal seizure‐like movements: A case report

Rahimi,

Amirifard,

Jameie

2024

Clinical Case Reports

View full text Add to dashboard Cite

Key Clinical MessageThis study suggests that severe obstructive sleep apnea can present as sleep‐related epileptic or non‐epileptic seizures. A detailed history and physical examination, along with polysomnography and video electroencephalography findings can lead to the correct diagnosis.AbstractObstructive sleep apnea (OSA) is defined by recurrent episodes of the upper airway complete or partial collapse while sleeping. The obstructive episodes result in gradual suffocation that increases breathing attempts till the person is awakened. The main manifestations are excessive daytime sleepiness, snoring, observed episodes of stopped breathing, and abrupt awakenings accompanied by gasping or choking. Nevertheless, there are very few reports of patients with OSA, manifesting other symptoms such as seizure‐like movements. Differentiating OSA with nocturnal seizures could be challenging due to their overlapping features. A 53‐year‐old man presented to the clinic, experiencing seizure‐like involuntary movements during nocturnal sleep for the past 2 years with a frequency of 2–3 times per night. Neurologic examinations were normal. Further evaluation with polysomnography revealed impaired arousal followed by seizure‐like movements during sleep. Video electroencephalography (EEG) did not show any epileptiform discharges, ruling out the nocturnal seizure diagnosis. The patient was diagnosed with OSA. Subsequently, continuous positive airway pressure (CPAP) treatment resolved all symptoms.

show abstract

Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep

Cited by 173 publications

References 39 publications

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

Interação entre o grupamento parafacial/núcleo retrotrapezóide e a região de kölliker-fuse na modulação do padrão respiratório.

An unusual presentation of severe obstructive sleep apnea with nocturnal seizure‐like movements: A case report

Contact Info

Product

Resources

About