Applied ionophoretically to central neurons, histamine produces either excitatory or inhibitory effects, via H1, H2 and H3 receptors all of which are typical G-protein coupled receptors.

H1- receptors are coupled to phospholipase C, and prodice mainly excitatory effects, whereas H2- receptors act cAMP formation, and are mainly inhibitory.

H3- receptors serve as inhibitory autoreceptors on histaminergic neurons.

The role of histamine in the CNS is poorly understood. Blocking H1- receptors causes sedation and also has antiemetic effect.