Histaminergic drugs as modulators of CNS function

The first indication that histamine might be important in the functioning of the brain was the finding that the centrally penetrating histamine H1 antagonists had marked sedative properties. Subsequently with the development of more specific compounds and drugs for the H1, H2 and H3 receptors a greater understanding of the neurotransmitter/modulator role of histamine in the CNS has been possible. Histamine is now associated with wakefulness, suppression of seizures, hypothermia and emesis. The histamine H1 antagonists have been shown to potentiate opioid-induced analgesia, and modify eating and drinking patterns as well as endocrine secretions from the pituitary gland. Additionally, clinically useful antidepressants have been shown to inhibit histamine-sensitive adenylate cyclase from the mammalian brain. Recently, a possible role for both histamine H1 and H2 receptors in schizophrenia has been reported. As more specific and centrally-penetrating histaminergic compounds are developed, so the roles of histamine as a neurotransmitter/modulator in the brain will be better understood.