[11C]Doxepin binding to histamine H1 receptors in living human brain: reproducibility during attentive waking and circadian rhythm

Abstract

Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET) enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride and [11C]FLB457 revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous [11C]raclopride studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test–retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (less than 10%) was not significant. Similarly, the binding potential of [11C]doxepin in the cerebral cortex was slightly higher in the morning than that in the afternoon, but it was also insignificant. These data suggest that higher histamine release during wakefulness could not decrease the [11C]doxepin binding in the brain. This study confirmed the reproducibility and reliability of [11C]doxepin in the previous imaging studies to measure the H1 receptor.

Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers

“…The difference in BPR of [ 11 C]doxepin binding was less than 10 % among several different PET scanning conditions. Accordingly, the test-retest reproducibility of [ 11 C]doxepin binding has been confirmed (Shibuya et al 2012).…”

11C‐labeled and 18F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain

“…Quantitative PET studies have been used successfully to correlate age with H 1 R densities, to show gender differences, and to demonstrate H 1 R alterations in disorders such as depression, schizophrenia, Alzheimer's disease, and anorexia nervosa . No evidence was found for a role of H 1 R in attentive waking and circadian rhythm …”

The effect of doxepin on Bacillus subtilis and Pseudomonas aeruginosa

“…Doxepin is a tricyclic antidepressant with a tertiary amine, inhibits the reuptake of serotonin and norepinephrine exerts a very low inhibition of dopamine reuptake. Doxepin is active metabolite of desmethyldoxepin (nordoxepin), has also antidepressant effects [1][2][3]. Doxepin was approved by the FDA in 2010 and is indicated for the treatment of insomnia characterized by difficulties with sleep maintenance.…”