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Targeting of the central histaminergic system for treatment of obesity and associated metabolic disorders
Author(s) -
Malmlöf Kjell,
Hohlweg Rolf,
Rimvall Karin
Publication year - 2006
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20140
Subject(s) - histaminergic , endocrinology , medicine , histamine , hypothalamus , arcuate nucleus , neurotransmitter , energy homeostasis , anorectic , obesity , biology , receptor , food intake
There is currently a need for effective pharmacological therapies for treatment of obesity. In this communication, the involvement of the neurotransmitter histamine in the regulation of food intake is reviewed, together with results obtained in animals with pharmacologically increased brain histamine levels. A survey of the literature reveals that histaminergic circuits, arising from nerve cell bodies in the tuberomammillary nucleus and projecting into the paraventricular nucleus, the arcuate nucleus, and the ventromedial hypothalamus, are strongly involved in regulation of food intake and possibly also energy expenditure. Current literature also suggests the histaminergic circuits connect to other neuronal pathways involved in the regulation of energy balance and body weight. Studies performed in rodents demonstrate that H 3 receptor antagonists increase hypothalamic histamine and decrease food intake, which result in decreased body weight. Lipid oxidation is increased and, at higher doses, body fat is also decreased. These changes are associated with lower circulating levels of insulin during an oral glucose challenge suggesting an increase in insulin sensitivity. The effects on food intake have also been confirmed in pigs and rhesus monkeys. It can thus be concluded that results obtained with H 3 antagonist in animals warrant future clinical studies to evaluate whether this principle is effective in the treatment of human obesity. Drug Dev. Res. 67:651–665, 2006. © 2006 Wiley‐Liss, Inc.