Histamine, an important bioactive molecule, is derived from the decarboxylation of the amino acid histidine. Most histamine in the body is generated in granules in mast cells and in skin, lung and gastrointestinal tract, playing a pivotal role in allergic and inflammatory reactions. Histamine acts as a neurotransmitter within the central nervous system. The histaminergic neurons that secrete histamine are localized in small regions of the hypothalamus, but those neurons send axons widely throughout the brain. Histamine appears to modulate a number of important processes in the brain, including wakefulness, cognitive ability and food consumption. Currently four histamine receptors (H1R-H4R) have been cloned and identified, all of which are G protein-coupled receptors. These different receptors are expressed on different cell types and work through different intracellular signaling mechanisms. Post mortem studies have revealed alterations in histaminergic system in neurological and psychiatric diseases.

Melatonin is a hormone, produced by the pineal gland, a tiny endocrine gland situated at the center of the brain. Melatonin presents several ways of action in the regulation of seasonal reproduction, body weight and energy balance, antiaging, and promoting sleep.