Disease relevance of Antalarmin

• We conclude that chronic administration of antalarmin does not affect body weight, carbohydrate metabolism, or leptin expression, whereas it reduces adrenocortical function mildly, without anatomical, clinical, or biochemical evidence of causing adrenal atrophy [1].
• The centrally acting CRF antagonist, antalarmin (32 mg/kg), produced elongation of the PR interval (p<0.0001), robust bradycardia (135+/-18; p<0.001), and increased sinking (92%; p<0.05), and methylatropine nitrate (3.2 mg/kg) blocked these effects [2].
• In addition, SSR125543A and antalarmin antagonized stress-induced hyperthermia, distress vocalization, and cortical norepinephrine release [3].
• In the current study we tested the hypothesis that a selective, non-peptide CRF1 receptor antagonist, antalarmin, would inhibit hypersensitivity in the WKY rat colon [4].
• Arthritis was induced in both antalarmin and vehicle treated LEW/N and F344/N rats by subcutaneous injections at the base of the tail of incomplete Freund's adjuvant containing 10 mg/ml heat killed Mycobacterium tuberculosis [5].

Psychiatry related information on Antalarmin

• Antalarmin also reversed yohimbine's anxiogenic effects in the social interaction test [6].

High impact information on Antalarmin

• We found that antalarmin, a CRH receptor type 1 antagonist, decreased FasL expression and promoted apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and inhibited by antalarmin [7].
• Embryos from mothers that lacked T cells or from syngeneic matings were not rejected when the mothers were given antalarmin [7].
• Female rats treated with antalarmin showed a marked decrease in implantation sites and live embryos and diminished endometrial FasL expression [7].
• Stress-induced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals [8].
• These effects appeared to be mediated via the R1 receptors because the CRH receptor antagonists, astressin and antalarmin but not anti-sauvagine 30, could block them [9].

Chemical compound and disease context of Antalarmin

• The ir-ACTH response to hypoxia was diminished (p < 0.05) in the antalarmin-treated fetuses while the cortisol responses of antalarmin- and vehicle-treated fetuses were indistinguishable [10].

Biological context of Antalarmin

• Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation [11].
• Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test) [12].
• Receptor autoradiography indicated an up-regulation of dopamine D2, but no change in D1, binding in striatum, and Golgi-Cox analysis of striatal medium spiny neurones indicated that chronic antalarmin treatment increased spine density [13].
• We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH [12].
• Collectively, these findings demonstrate that multiple signalling systems are susceptible to modulation by social isolation and that antalarmin can reverse some, but not all, isolation-induced alterations in brain chemistry [14].

Anatomical context of Antalarmin

• After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose [11].
• Human adrenal cortical and/or chromaffin cells in co-culture were incubated with CRH, antalarmin, and both CRH and antalarmin in vitro [15].
• The width of the adrenal cortex of animals treated with antalarmin was reduced by 31% compared with that in controls without atrophy of the gland [1].
• Of chief interest was whether the CRH-R1-selective pyrrolopyrimidine, antalarmin, shown previously to have activity in the central nervous system (CNS), would differ in its antagonist profile from the CRH-R1- & 2-selective peptide, astressin B, which is unlikely to have access to the CNS following systemic administration [16].
• Thus, chronic antalarmin treatment modulates dopaminergic pathways and implies that chronic treatment with drugs of this class may ultimately alter postsynaptic signaling mechanisms within the basal ganglia [13].

Associations of Antalarmin with other chemical compounds

• Fluoxetine, bupropion, diazepam and antalarmin all suppressed stress-induced gastric ulceration in male Sprague-Dawley rats exposed to four hours of plain immobilization [17].
• Following a 2-hour period of withdrawal, dependent and nondependent animals were systemically administered antalarmin, MJL-1-109-2, or R121919 (CRF(1) antagonists) and ethanol self-administration was measured [18].
• Compounds such as CP 154,526 (12), NBI 27914 (129) and Antalarmin (154) inhibit CRF-stimulation of cAMP or CRF-stimulated ACTH release from cultured rat anterior pituitary cells [19].
• The plasma cortisol responses of antalarmin- and vehicle-treated fetuses to exogenous ACTH(1-24) were indistinguishable [10].
• Fetuses received antalarmin (15 mg/h i.v.) or vehicle (cremophor El 50% in ethanol) from day 130 gestational age [10].

Gene context of Antalarmin

• CRH inhibited EVT invasion in Matrigel invasion assays, and this effect was blocked by the CRH receptor type 1 (CRHR1)-specific antagonist antalarmin [20].
• The action of CRH was completely inhibited by antalarmin [15].
• We previously showed that acute stress increases rat blood-brain barrier (BBB) permeability, an effect involving brain mast cells and CRF, as it was absent in W/W(v) mast cell-deficient mice and was blocked by the CRF-receptor antagonist, Antalarmin [21].
• The performance-enhancing effects of Ucn in both water maze and passive avoidance paradigms were reversed by i.c.v. pretreatment with D-Phe CRF(12-41) (2.5, 5 microg), a broad CRF(1)/CRF(2) receptor antagonist, or antalarmin (10 microg), a potent, nonpeptide, CRF(1) selective receptor antagonist [22].
• These effects were mediated by the CRH type 1 receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression [23].

Analytical, diagnostic and therapeutic context of Antalarmin

• A selective CRH-R1 antagonist (antalarmin, 10-20 mg/kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line [8].
• METHODS: F344/N and LEW/N rats were assigned to either drug or vehicle groups and treated with 20 mg/kg antalarmin or vehicle alone BID for 25 days by intraperitoneal injection [5].
• The 10-day-long intravenous administration of antalarmin, a CRH receptor antagonist, significantly prolonged gestation compared to the control group of animals [24].
• The CRFR1 antagonist antalarmin inhibited the [(3)H]DA release induced by electrical stimulation and enhanced by CRF and Ucn I [25].
• A simple and rapid method was developed for the quantitation of antalarmin from plasma using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (ESI/MS) [26].

References