Beyond depression and anxiety; a systematic review about the role of corticotropin-releasing hormone antagonists in diseases of the pelvic and abdominal organs

Abstract

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.

Evaluation of IL-8 and IL-10 Levels in men with Irritable Bowel Syndrome

“…The low level of IL-10 in colon patients may be due to a genetic disorder and genetic defects in the IL-10 / IL-10R pathway, as they develop acute early colitis [64]. This indicates that IL-10 plays an important role in maintaining the normal immune tolerance of the gut and that its reduction causes immune disturbance and inflammation that may lead to symptoms of IBS [65].As for the comparison among age groups of people with irritable bowel syndrome, the results of the current study showed a statistically significant difference among them, as the age group (50-41) was the least significant, and this was in consistency with the study of [66,67] .The study of [66]included 108 patients with colon disorders divided into two groups of ages (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) and the duration of the disease was 6 years. The reason for this may be the abnormal immune regula...…”

“…The current study showed that the high level of interleukin-8 in patients with irritable bowel may have a major role in the pathogenesis of the disease, as irritable bowel syndrome (IBS) was previously considered a psychosomatic disorder, but recent studies such as [22,23]. indicated that inflammation plays an important role in colon irritation, as the studies confirmed changes in Mast cell (MC), T lymphocytes and B lymphocytes, and showed higher concentrations of cytokines in the colon mucosa and in the blood of patients with Irritable Bowel Syndrome, compared to healthy subjects [24].…”

Metabolic Adverse Effects of Psychotropic Drug Therapy: A Systematic Review

“…1 to 10% risk of metabolic disorders [25]. 16.9% to 22.9% risk of gastrointestinal disturbance [26].…”

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

“…They have yet brought plenty of problems, such as high affinity, long elimination half-life, active metabolites, high protein binding, pre-clinical screening, mismatch between dynamic characteristics of CRHR function and subject patients, acute versus advanced manifestations of the disease; NBI-77860 has the side effect of headache; R121919 significantly reduces the score of depressive patients, but the relevant study lacks blind, randomized, or placebo-controlled controls and causes elevated liver enzymes; there was no significant difference between CP-316,311 and placebo treatment. 119 - 121 In addition, the balance between receptor affinity and the pharmacokinetic property of CRHR1 antagonists remains the focus of the pharmaceutical industry. 114 Besides, CRHR2 agonists have an anti-anxiety effect in CNS, but can delay gastric empty, therefore, organ-selective CRHR2 agonists should be chosen in clinic.…”