Neuroimaging of mirtazapine enantiomers in humans

Abstract

Mirtazapine is a racemic antidepressant with a multireceptor profile. Previous studies have shown that the enantiomers of mirtazapine have different pharmacologic effects in the brain of laboratory animals. In the present study, we used positron emission tomography (PET) and autoradiography to study effects of (R)- and (S)-[(11)C]mirtazapine in the human brain. Detailed brain imaging by PET using three methods of kinetic data analysis showed no reliable differences between regional binding potentials of (R)- and (S)-[(11)C]mirtazapine in healthy subjects. Autoradiographic studies carried out in whole hemispheres of human brain tissue showed, however, that (R)- and (S)-mirtazapine differ markedly as inhibitors of [(3)H]clonidine binding at alpha(2)-adrenoceptors. The multireceptor binding profiles of mirtazapine enantiomers, along with individual differences between subjects, may preclude PET neuroimaging from demonstrating reliable differences between the regional distribution and binding of (R)- and (S)-[(11)C]mirtazapine in the living human brain.