dora-22

Description: DORA-22 is a novel, potent and selective dual orexin receptor antagonist that may be useful for insomnia and AD-relevant symptoms. It can lower histamine levels in the lateral hypothalamus and prefrontal cortex without lowering hippocampal acetylcholine. DORA-22 suppresses the release of the wake neurotransmitter histamine in the lateral hypothalamus, prefrontal cortex, and hippocampus with no significant alterations in acetylcholine levels. Compared with the GABAA modulator eszopiclone, DORA-22 elicits a neurotransmitter profile consistent with wake reduction that does not impinge on neurotransmitter levels associated with cognition and rapid eye movement sleep. DORAs may improve sleep in AD patients. Further investigations should optimize the dose and duration of DORA-22 treatment and explore additional AD-relevant animal models and cognitive tests.

References: Alzheimers Dement (N Y). 2019 Feb 28; 5:70-80; J Neurochem. 2017 Jul; 142(2):204-214.