The histaminergic network in the brain: basic organization and role in disease

The histaminergic system is implicated in various brain disorders. A mutation in the gene encoding histidine decarboxylase, the histamine synthesizing enzyme, has been identified to be a cause of dominantly inherited Guilles de la Tourette syndrome.In clinical trials, histamine H2 receptor antagonists have shown therapeutic efficacy for schizophrenia. and histamine H3 receptor antagonists have shown promise for combating daytime sleepiness in patients with narcolepsy.In experimental allergic encephalomyelitis, a mouse model of multiple sclerosis, animals lacking histidine decarboxylase (and hence histamine synthesis) or histamine receptors show abnormal development of disease symptoms.Histamine regulates feeding, obesity and the actions of leptin via histamine H1 receptor signalling in the hypothalamus; antipsychotic drugs bind to H1 receptors and cause obesity through this mechanism.Histamine H3 receptor antagonists regulate alcohol self-administration and conditioned place preference in rodents, probably through a modulatory action on dopaminergic signalling. These drugs have already been tested for other disease conditions, so clinical trials on alcoholism could be carried out without extensive early phase studies.