Serotonin and substance P: Synergy or competition in the control of breathing

Szereda-Przestaszewska, Małgorzata; Kaczyńska, Katarzyna

doi:10.1016/j.autneu.2020.102658

Cited by 16 publications

(19 citation statements)

References 110 publications

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“…SP is also a regulatory neuropeptide that control the ventilatory responses in humans. They are expressed in several brainstem nuclei where they regulate the respiratory rhythm at central or peripheral level as well as within the airways and lungs [45] , [46] .…”

Section: Introductionmentioning

confidence: 99%

Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment

Mehboob¹

2021

Biomedicine & Pharmacotherapy

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Novel Coronavirus infection (COVID-19) has become a pandemic in these days. It is an acute respiratory and infectious disease with no known etiology and treatment. It is continuously causing losses of precious lives and economy at a global scale on daily basis. It is the need of the hour to find more treatment strategies by either developing a drug or to boost the immune system. This opinion article aims to provide Substance P (SP) as a possible cause of the initiation of cytokine storm developed in COVID-19 infection and to suggest Neurokinin-1 Receptor (NK-1R) antagonist, Aprepitant, as a drug to be used for its treatment. This perspective will provide directions to the Biomedical scientists to explore SP and NK-1R and prepare a drug to alleviate the symptoms and cure the disease. It is very important to work on this perspective at earliest to reach to some conclusion regarding the therapeutic intervention. Clinical studies may also be conducted if proven successful. SP is a neurotransmitter and neuromodulator, released from the trigeminal nerve of brainstem as a result of nociception. It is directly related to the respiratory illness as is in COVID-19 infection. It is responsible for the increased inflammation and the signature symptoms associated with this disease. It is the main switch that needs to be switched off by administering Aprepitant along with glucocorticosteroid, dexamethasone.

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Section: Introductionmentioning

confidence: 99%

Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment

Mehboob¹

2021

Biomedicine & Pharmacotherapy

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“…Some of our recent unpublished work also reports similar findings of SP/NK-1R involvement in inflammation 23 , pain, pathologies, sudden deaths 24 etc. SP and NK-1R are also found to be involved in immunology 7, 15 , lung inflammation 2, 7 , respiratory network stability 25, 26 , heart failure 27 and neurological and psychiatric disorders 28 . An increased expression of SP in plasma of patients with other viral infections such as HIV and HSV is also well documented 6, 29 .…”

Section: Introductionmentioning

confidence: 99%

Aprepitant as a combinant with Dexamethasone reduces the inflammation via Neurokinin 1 Receptor Antagonism in severe to critical Covid-19 patients and potentiates respiratory recovery: A novel therapeutic approach

Mehboob

Ahmad

Qayyum³

et al. 2020

Preprint

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Background: Corona virus infection is a respiratory infection, compromising the normal breathing in critical patients by damaging the lungs. Researches are ongoing to find an efficient treatment strategy for this disease by either inactivating the virus or boosting the immune system of patient or by managing the cytokine storm. Aim: To evaluate the clinical outcomes of Substance P receptor Neurokinin 1 antagonist in Covid 19 patients against the usual treatments as controls. Patients and Methods: It is a randomized clinical trial, open label, having two arms, one receiving normal management and care while other receiving Neurokinin 1 Receptor antagonist, Aprepitant, in addition. Dexamethasone, a corticosteroid is also administered orally to both the groups. PCR positive, hospitalized patients with more than 18 years of age, both genders, moderate to critical phase were included. 18 patients were randomly allocated in both arms, having 10 in group A and 8 in group B. Lab investigations were performed in both the groups before and after the intervention. We report preliminary results for the comparison of Aprepitant 80 mg given once daily for 3 to 5 days vs routine management. The primary outcome was total in hospital days and duration of disease. Results: Mean age of patients in group A was 47.63 +12.07years while 60.90+ 9.75 years in group B. There were 3 males in group A and 8 in group B. There were 2 critical patients in group A and 5 in group B. Biochemical and hematological parameters in both groups didnot show much difference except the C reactive protein reduction in the intervention group, indicative of a reduced inflammation. Oxygen saturation also improved but more patients should be enrolled to get a statistically significant data. One patient was discharged from each group within 5 days and one patient expired in each. Conclusions: It is a pilot study but the findings give a strong clue for the therapeutic potential of Aprepitant. Patients who received a combination therapy of Aprepitant and Dexamethasone were recovered earlier and showed improved clinical outcomes, laboratory findings and reduced C reactive protein which is an inflammatory marker. We suggest here a study on larger sample size to get a deeper insight of its potential and efficacy. It may be more effective in severe to critical patients having respiratory difficulties.

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“…Respiratory rhythm regulation is the main role of SP which is evidenced through many studies [14,17]. SP along with serotonin is found to be innervating the medullary motoneurons involved in upper airways [7]. It was also found to be a sensory neurotransmitter in the laryngeal afferent system [18].…”

Section: Introductionmentioning

confidence: 97%

“…It aggravates the condition by its over secretion by TG neurons which affects the immune cells as well as other cells in respiratory tract to release the mediators for cytokine storming which is responsible for further complications. The ventilatory role of SP is well established [7]. There may be less unlikely possibility of latency in SARS-Cov-2 and this virus may reach the TG via TrN in eyes, nose and mouth and controls the release of peptides including SP.…”

Section: Introductionmentioning

confidence: 99%

<strong>SARS-Corona Virus-2 May Initially Infect Brainstem through Trigeminal Ganglion-Latency May Be Present-A New Perspective </strong>

Mehboob¹,

Ahmad²

2020

Preprint

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Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.

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Serotonin and substance P: Synergy or competition in the control of breathing

Cited by 16 publications

References 110 publications

Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment

Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment

Aprepitant as a combinant with Dexamethasone reduces the inflammation via Neurokinin 1 Receptor Antagonism in severe to critical Covid-19 patients and potentiates respiratory recovery: A novel therapeutic approach

<strong>SARS-Corona Virus-2 May Initially Infect Brainstem through Trigeminal Ganglion-Latency May Be Present-A New Perspective </strong>

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