MAPPING OF HISTAMINE H1 RECEPTORS IN THE HUMAN BRAIN USING [C-11] PYRILAMINE AND POSITRON EMISSION TOMOGRAPHY

We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H-1 receptors in human brain with positron emission tomography (PET). [C-11]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), C-11 radioactivity was observed at high concentrations in the frontal and temporal cortex, hipPocampus, and thalamus. and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H-1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H-1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H-1 receptors are. thought to be abnormal.