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Pathway Description
Histamine Neurological Sleep Pathway
Homo sapiens
Physiological Pathway
H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Doxylamine inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness.
References
Histamine Neurological Sleep Pathway References
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.
Pubmed: 17139284
Thakkar MM: Histamine in the regulation of wakefulness. Sleep Med Rev. 2011 Feb;15(1):65-74. doi: 10.1016/j.smrv.2010.06.004. Epub 2010 Sep 20.
Pubmed: 20851648
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.
Pubmed: 17016423
Passani MB, Lin JS, Hancock A, Crochet S, Blandina P: The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders. Trends Pharmacol Sci. 2004 Dec;25(12):618-25. doi: 10.1016/j.tips.2004.10.003.
Pubmed: 15530639
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