fear

TCS 1102 is an effective, dual orexin receptor antagonist (Ki: 0.2 3 nM for OX2 1 receptors).

DO34 is a selective and potent diacylglycerol lipase (DAGL-α β) inhibitor that impairs fear extinction in mice, and can be used to study lipopolysaccharide inflammatory pain.

CB1 antagonist 4 is an antagonist of cannabinoid receptor type 1 (CB1), with potential for the treatment of obesity and type 2 diabetes.

Ogerin is a selective GPR68 positive allosteric modulator (pEC50: 6.83) that blocks recall in fear conditioning in mice. It exhibits inverse agonist and antagonist activity (Ki, 220 nM) at the A2A receptor and weak antagonist activity (Ki, 736 nM) at the 5-HT2B receptor.

PF-05180999 (PF-999) is a selective and potent phosphodiesterase 2A (PDE2A) inhibitor that enhances long-term memory in a contextual fear conditioned reflex model in rats.

Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.

Fluoroethylnormemantine hydrochloride, a Memantine derivative, functions as an antagonist for the N-methyl-D-aspartate (NMDA) receptor. It can also serve as a positron emission tomography (PET) tracer, specifically as [18F]-Fluoroethylnormemantine hydrochloride. Notably, this compound displays a range of effects, including anti-amnesic, neuroprotective, antidepressant-like, and fear-attenuating properties.

Fluoroethylnormemantine, a derivative of Memantine, acts as an N-methyl-D-aspartate (NMDA) receptor antagonist and can function as a positron emission tomography (PET) tracer known as [18F]-fluoroethylnormemantine. This compound displays anti-amnesic, neuroprotective, antidepressant-like, and fear-attenuating properties.

MS21570 as a GPR171 antagonist based on its ability to block,with an IC50 of 220 Nm,that reduces anxiety-like behavior and fear conditioning in mice.

CNQX (FG9065) is a competitive, non-NMDA glutamate receptor antagonist (IC50s = 0.3 and 1.5 μM for AMPA and kainate receptors, respectively)

Trofinetide, derived from the neuroprotective tripeptide Gly-Pro-Glu (an N-terminal sequence of insulin-like growth factor-1, IGF-1), shows promise in various neuroprotective models. At a concentration of 10 nM, it mitigates cell death in primary rat embryonic striatal neurons caused by okadaic acid. Additionally, Trofinetide reduces the expression of pro-inflammatory markers (IL-1β, TNF-α, IL-6, and E-selectin) in a rat model simulating neuroinflammation from penetrating ballistic-like brain injuries. In cases of brain injury induced by middle cerebral artery occlusion (MCAO), administration of Trofinetide at 30 and 60 mg kg reduces the area of cortical and striatal infarct. Furthermore, a daily dose of 100 mg kg reverses social recognition and contextual fear conditioning deficits, diminishes the number of dendritic spines, and decreases testicular weight gain in an fmr1- - knockout mouse model of fragile X syndrome. Trofinetide formulations have been employed in treating Rett syndrome, highlighting its versatility across various neurological conditions.

CNQX disodium is a competitive non-NMDA receptor antagonist and competitive AMPA kainate receptor antagonist in neuronal cultures.

Mammalian bombesin-like peptide neurotransmitter that is an agonist for the gastrin-releasing peptide receptor (GRPR). GRP has been reported to activate GABAergic interneurons in the amygdala leading to increased GABA release and fear suppression in mice

Potent, selective and competitive corticotropin-releasing factor CRF2 receptor antagonist (Kd values are 1.4 and 153.6 nM for binding to mouse CRF2β and rat CRF1 receptors respectively). Inhibits sauvagine-stimulated cAMP accumulation in HEK-mCRF2β cells