Validation of Brain Angiotensin System Blockade as a Novel Drug Target in Pharmacological Treatment of Neuropsychiatric Disorders

Wincewicz, Dominik; Braszko, Jan J.

doi:10.1055/s-0043-112345

Cited by 12 publications

(7 citation statements)

References 188 publications

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“…In the presence of D4 receptor blockade with clozapine or olanzapine, it is likely that the natriuretic effects of ARBs will be increased, further supporting the concept of treating hypertension associated with antipsychotic dopamine receptor antagonists. Of note, a recent review suggest that inhibition of the brain angiotensin system can reduce psychosis, thus complementing the antipsychotic actions of D2‐like receptor antagonists . The mutant mouse with a non‐functional D2 receptor mutation also has increased BP due to increased vasoconstrictor effects of sympathetic nervous system activation and endothelin type B receptor activation …”

Section: Resultsmentioning

confidence: 99%

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure

et al. 2017

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SummaryWhat is known and Objective: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist. Methods:A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords: hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion.Results and Discussion: All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors. What is new and

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Section: Resultsmentioning

confidence: 99%

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure

et al. 2017

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“…The protective effects exerted by ACEIs and ARBs treatments in pre-clinical and clinical settings have supported the involvement of RAS in neuropsychiatric conditions as well ( 51 , 70 , 71 ). In animal models of Parkinson's disease induced by MPTP or 6-hydroxydopamine, administration of AT1 receptor antagonists like losartan and ACEIs such as perindopril prevented motor dysfunction and resulted in increased dopamine striatal levels and neuronal survival ( 72 – 76 ).…”

Section: Ace2-angiotensin (1-7)-mas Receptors Axis Role In Geriatric-mentioning

confidence: 88%

“…ACEIs and ARBs are commonly prescribed for hypertension, myocardial infarction, heart failure, and diabetic nephropathy ( 98 – 100 ). The discovery of the expression of RAS components in the brain stimulated the investigation of the potential effects of ACE inhibition and AT1 receptor antagonism on the physiopathology of neuropsychiatric disorders ( 71 ).…”

Section: Discussion: Challenges and Opportunitiesmentioning

confidence: 99%

Coronavirus Disease-2019 Conundrum: RAS Blockade and Geriatric-Associated Neuropsychiatric Disorders

Miranda

Teixeira

2020

Front. Med.

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Coronavirus Disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily targets the human respiratory system and may lead to severe pneumonia and ultimately death. Mortality rate is particurlarly high among people beyond the sixth decade of life with cardiovascular and metabolic diseases. The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic. Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.

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“…In addition, evidence suggests that an abrupt suspension of ACE inhibitors in patients with COVID-19 and cardiovascular disease may result in clinical deterioration and worse outcomes ( 136 , 138 , 139 ). In addition, the results of some preclinical studies suggested that ACE inhibition shows promise in the mitigation of psychotic symptomatology and cognitive deficits ( 140 – 142 ). Furthermore, human studies have indicated that ACE inhibitors may have favorable effects on cognitive deficits in schizophrenia, possibly by modulating the cleavage of specific neuropeptides, such as substance P and neurotensin ( 141 , 142 ).…”

Section: Ace Polymorphismsmentioning

confidence: 99%

“…In addition, the results of some preclinical studies suggested that ACE inhibition shows promise in the mitigation of psychotic symptomatology and cognitive deficits ( 140 – 142 ). Furthermore, human studies have indicated that ACE inhibitors may have favorable effects on cognitive deficits in schizophrenia, possibly by modulating the cleavage of specific neuropeptides, such as substance P and neurotensin ( 141 , 142 ).…”

Section: Ace Polymorphismsmentioning

confidence: 99%

Dysregulated inflammation may predispose patients with serious mental illnesses to severe COVID‑19 (Review)

et al. 2021

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Genetic and nongenetic factors associated with an increased inflammatory response may mediate a link between severe coronavirus disease 2019 (coVid-19) and serious mental illness (SMi). However, systematic assessment of inflammatory response-related factors associated with SMI that could influence COVID-19 outcomes is lacking. In the present review, dietary patterns, smoking and the use of psychotropic medications are discussed as potential extrinsic risk factors and angiotensin-converting enzyme (ace) insertion/deletion (i/d) gene polymorphisms are considered as potential intrinsic risk factors. a genetics-based prediction model for SMi using ace-i/d genotyping is also proposed for use in patients experiencing severe coVid-19. Furthermore, the literature suggests that ace inhibitors may have protective effects against SMi or severe coVid-19, which is often linked to hypertension and other cardiovascular comorbidities. For this reason, we hypothesize that using these medications to treat patients with severe coVid-19 might yield improved outcomes, including in the context of SMi associated with coVid-19. Contents1. introduction 2. Psychotropic medications as possible modulators of coVid-19 severity with existing SMi 3. dietary factors as possible modulators of coVid-19 severity among patients with SMi 4. cigarette smoking as a possible modulator of coVid-19 severity among patients with SMi 5. ace polymorphisms 6. conclusion

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Validation of Brain Angiotensin System Blockade as a Novel Drug Target in Pharmacological Treatment of Neuropsychiatric Disorders

Cited by 12 publications

References 188 publications

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure

Coronavirus Disease-2019 Conundrum: RAS Blockade and Geriatric-Associated Neuropsychiatric Disorders

Dysregulated inflammation may predispose patients with serious mental illnesses to severe COVID‑19 (Review)

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