Antalarmin HCl is a non-peptide CRHR1 antagonist with a Ki value of 1 nM. Antalarmin HCl inhibits CRH-induced ACTH secretion, and blocks CRH- and novel-object-induced anxiety-like behaviours in animal model. Antalarmin HCl produces an anti-inflammatory effect in a model of arthritis and inhibits the pressure-induced gastric ulcers associated with irritable bowel syndrome[1][2][3].
Antalarmin HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
COS-M6 cells
10 µM
15 min
Measure intracellular cAMP levels, Antalarmin blocks the constitutive activation of CRF(1–16)-R1DN chimera in a dose-dependent manner
Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10277-81
dlBnST neurons
40 or 4μM
45 min
To test the effect of antalarmin on the frequency of GABA A receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). Results showed that antalarmin significantly reduced the frequency of sIPSCs in the AAS-treated group, reversing the AAS-induced enhancement of GABAergic inhibition.
Neuropsychopharmacology. 2012 May;37(6):1483-99
Antalarmin HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Balb/c mice
Orthotopic injection of 4T1 cells in the mammary fat pad to induce breast tumors
Intraperitoneal injection
20 mg/kg
Daily for 6 weeks
To assess the impact of peripheral CRF inhibition on stress-induced tumor growth, results showed that Antalarmin suppressed stress-induced tumor growth and neoangiogenesis.
Mol Cancer. 2010 Sep 27;9:261
Sprague-Dawley rats
Stress and anxiety-related behavior model
Intraperitoneal injection
20 mg/kg
Single administration
To evaluate whether antalarmin could mitigate the attention deficits induced by PACAP. Results showed that antalarmin attenuated, but did not completely reverse, the effects of PACAP.
Biol Psychiatry. 2016 Dec 15;80(12):955-964
Rats
Ethanol-dependent model
Intraperitoneal injection
10 or 20 mg/kg
Single administration, 1 hour (80 minutes) prior to testing
Antalarmin significantly reduced ethanol self-administration in ethanol-dependent rats during acute withdrawal but had no effect in nondependent rats.
Biol Psychiatry. 2007 Jan 1;61(1):78-86
Adult male rhesus macaques
Social stress model (intruder paradigm)
Oral
20 mg/kg
Single dose, behavioral assessment 150 minutes post-administration
To evaluate the effects of Antalarmin on behavioral, neuroendocrine, and autonomic responses to stress in rhesus macaques. Results showed that Antalarmin significantly reduced anxiety and fear-related behaviors, increased exploratory and sexual behaviors, and significantly attenuated the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress.
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6079-84
Mice
Environmental switch model
Intraperitoneal injection
10 mg/kg
Twice daily for 7 days
Blockade of CRF1R completely eliminated the enhancement of cocaine rewarding effects induced by environmental switch
Neuropsychopharmacology. 2012 Jun;37(7):1579-87
Rats
Swim stress model
Intraperitoneal injection
32 mg/kg
Single administration, swim test lasted for 2 hours
To evaluate the effect of Antalarmin on cardiac vagal activity during swim stress. Results showed that Antalarmin significantly prolonged PR interval, induced severe bradycardia, and increased the percentage of sinking rats. These effects were blocked by methylatropine nitrate.
Neuropsychopharmacology. 2006 Dec;31(12):2580-90
Wistar rats
Fear memory retrieval model
Intra-MRN injection
250 ng
Single injection, 10 minutes before
To evaluate the role of CRF1 receptor in fear memory retrieval, results showed no significant effect of Antalarmin on freezing behavior
Neuropsychopharmacology. 2010 May;35(6):1271-8
Female C57BL/6J mice
Chronic AAS exposure-induced anxiety-like behavior model
Intracerebroventricular (i.c.v.) infusion
10 mg/kg
Single injection, 5 minutes before testing
To evaluate the blocking effect of antalarmin on AAS-induced anxiety-like behaviors. Results showed that antalarmin significantly blocked the AAS-induced increase in ASR amplitudes, indicating that CRF-R1 signaling plays a key role in AAS-induced anxiety.
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