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Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. [1] The pentad symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS), and cataplexy. [1]
Orexin (/ ɒ ˈ r ɛ k s ɪ n /), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. [5] It exists in the forms of orexin-A and orexin-B.The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells ...
The rhesus monkeys were split into a test group and into a control group. The test group was administered orexin-A, intravenously or nasally. The control group was given a placebo. The sleep-deprived monkeys which were given the nasal form of orexin-A performed far better than the ones treated with injections.
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Both orexin receptors exhibit a similar pharmacology – the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.
In this simplified brain circuit, damage to orexin-secreting neurons in the hypothalamus can lead to inhibition of motor neurons, thus lowering muscle tone.. Cataplexy is considered secondary when it is due to specific lesions in the brain that cause a depletion of the hypocretin neurotransmitter.