In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation.

doi:10.1210/ENDO.137.12.8940412

Paper

In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation.

Published Dec 1, 1996 · E. Webster, D. Lewis, D. Torpy

Endocrinology

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296

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22

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Abstract

Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. CRH receptors (CRH-R1, R2alpha, R2beta) exhibit a specific tissue distribution. Antalarmin, a novel pyrrolopyrimidine compound, displaced 12SI-oCRH binding in rat pituitary, frontal cortex and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmnin (20 mg/kg body wt.) significantly inhibited CRH-stimulated ACTH release and carageenin-induced subcutaneous inflammation in rats. Antalarmin, or its analogs, hold therapeutic promise in disorders with putative CRH hypersecretion, such as melancholic depression and inflammatory disorders.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

Antalarmin, a novel pyrrolopyrimidine compound, effectively inhibits corticotropin-releasing hormone-stimulated ACTH release and peripheral inflammation in rats, offering potential therapeutic benefits for disorders involving CRH hypersecretion.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation.

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References

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Astressin is a potent, structurally constrained antagonist of corticotropin-releasing factor, with a 30x higher potency than the standard antagonist and 300x more potent than its linear analog in reducing hypophyseal corticotropin secretion in stressed rats.

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There is a high-affinity population of corticotrophin-releasing hormone binding sites in the human placenta, similar to those in the pituitary and myometrium, and their properties change in response to labor, suggesting placental CRH may regulate its receptor.

Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus.

Endometrial CRH may play a role in the implantation of blastocysts in early pregnant rat uterus, as it is expressed at implantation sites compared to inter-implantation regions.

Citations

Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice

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CRHR1 antagonist alleviated depression-like behavior by downregulating p62 in a rat model of post-stroke depression

A CRHR1 antagonist can alleviate depression-like behavior in post-stroke depression by inhibiting p62 expression and promoting its clearance in a rat model.

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Stress‐related neuropeptide systems as targets for treatment of alcohol addiction: A clinical perspective

Novel medications targeting stress-related neuropeptide systems show potential for treating alcohol addiction.

Effects of intracerebroventricular injection of corticotrophin releasing factor on the gene expression of ghrelin and corticotrophin releasing factor receptors in broiler chickens

Intracerebral injection of 10 g CRF increased ghrelin expression in the hypothalamus and CRFR1 expression in the small intestine, leading to a suppressed feed intake in broiler chickens.

Interplay Between the Immune and Endocrine Systems in the Lung: Implications for TB Susceptibility

Understanding the interactions between immune and endocrine systems in the lung may lead to new host-directed therapies for infectious diseases like tuberculosis and diabetes.

Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?

Ketamine's potential as a fast-acting antidepressant in treatment-resistant depression could improve our understanding of its etiology and potentially lead to a cure.

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The stress-axis system plays a crucial role in maintaining health, and early-life gut microbiome disturbances may alter stress response network development, potentially predisposing individuals to diseases later in life.