Obesity

Obesity is a global health crisis that results from poor diet and lack of sufficient physical activity that contributes to a number of pathologies including hypertension, coronary heart disease, diabetes, stroke, and cancer. An additional challenge to the rationale for antiobesity activity of H₃ receptor antagonists comes from findings that H₃ receptor agonists have appetite suppressant and weight loss effects in rodent models. The histamine H₃ receptor is predominantly expressed in the rodent central nervous system, with high levels of mRNA and receptor-binding sites detected in cortical areas as well as in other brain regions innervated by histaminergic neurons including the hypothalamus, hippocampus, nucleus accumbens, and striatum. Histamine has been known for a long time to play a critical role in homeostatic regulatory functions such as the control of food consumption and body weight regulation in animals. Neuronal input to hypothalamic histamine neurons originates from cortical, septal, and other hypothalamic areas.