Abstract
Evidence exists to implicate the monoamine histamine in the control of arousal and cognitive functions. Antagonists of H 3 receptors are postsynaptic and presynaptic modulators of neural transmission in a variety of neuronal circuits relevant to cognition. Accumulating neuroanatomical, neurochemical, pharmacological, and behavioral data support the idea that H 3 receptor antagonists may function to improve cognitive performances in disease states (e.g., Alzheimer's disease and mild cognitive impairment states). Thus, H 3 receptor antagonists have been shown to increase performance in attention and memory tests in nonhuman experiments and prevent the degradation in performances produced by scopolamine, MK-801, or age. In contrast, agonists of the H 3 receptor generally produce cognitive impairing effects in animal models. The role of H 3 receptors in these behavioral effects is substantiated by data indicating a central origin for their effects, the selectivity of some of the H 3 receptor antagonists studied, and the pharmacological modification of effects of H 3 receptor antagonists by selective H 3 receptor agonists. Data and issues that challenge the potential role for H 3 receptor antagonists in cognitive processes are also critically reviewed. H 3 receptor antagonists may also have therapeutic value in the management of obesity, pain, sleep disorders, schizophrenia, and attention deficit hyperactivity disorder.
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