Histamine and Appetite

Our survival relies on the ability to search for food to meet immediate metabolic needs and to store excess energy in the form of fat to meet metabolic demands during fasting. Hunger and satiety are key factors driving eating behavior and are under the control of a complex interplay between several central and peripheral neuroendocrine systems. Interest in the control of feeding has increased because of the obesity epidemic and rising incidence of metabolic diseases. The first evidence of the involvement of brain histaminergic system in the regulation of feeding dates to the 1970s. Since then, many studies ensued and up-to-date evidence suggests an inverse relationship between neuronal histamine and food intake. Preclinical studies demonstrated that brain histamine is released during both the appetitive and consummatory phases of feeding behavior and is also involved in the control of peripheral mechanisms regulating energy expenditure. Hypothalamic histaminergic receptors are crucial for the regulation of the diurnal rhythm of food consumption; furthermore, these receptors have been specifically recognized as mediators of energy intake and expenditure. All these features point to the histaminergic system as an attractive target for the development of new anti-obesity drugs. Despite preclinical encouraging data, though, clinical trials with histaminergic ligands did not meet the expectations. Not all is lost though, as recent clinical trials demonstrated the potential of betahistine (an H1 agonist/H3 antagonist) in opposing metabolic side effects associated with chronic antipsychotic treatments.