Positron emission tomographic analysis of dose-dependent NAD-299 binding to 5-hydroxytryptamine-1A receptors in the human brain.

Rationale: The serotonin 5-HT(1A) receptor has been ascribed a putative role in the pathophysiology and drug treatment of depression. NAD-299 (generic name robalzotan) is a new potential antidepressant with high affinity and selectivity for the 5-HT(1A) receptor.

Objectives: The aim of this positron emission tomography (PET) study was to examine the extent and time-course of 5-HT(1A) occupancy by NAD-299 in the human brain, in relation to plasma concentration after escalating single oral doses.

PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor.

NAD-299 is a selective 5-HT(1A) receptor antagonist that is currently developed as a putative antidepressant drug. [(11)C]NAD-299 was examined in the cynomolgus monkey brain with positron emission tomography (PET). After radioligand injection high accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, regions known to contain a high density of 5-HT(1A) receptors.

Use of PET and the radioligand [carbonyl-(11)C]WAY-100635 in psychotropic drug development.

Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine(1A) (5-HT(1A)) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT(1A) receptor now benefits from the highly selective radioligand [carbonyl-(11)C]WAY-100635 (WAY) for quantitative determination of 5-HT(1A) receptors in the primate and human brain in vivo using PET.

Synthesis of novel 5-substituted 3-amino-3,4-dihydro-2H-1-benzopyran derivatives and their interactions with the 5-HT1A receptor.

A series of new enantiomerically pure 3-amino-3,4-dihydro-2H-1-benzopyrans (3-aminochromans) has been synthesized from (R)- and (S)-5-methoxy-3-amino-3,4-dihydro-2H-1-benzopyran. The absolute configuration of the respective (R)- and (S)-enantiomers was deduced from X-ray crystallography of (R)-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran, (R)-9a. Various 5-substituents were introduced via palladium-catalyzed carbonylation of N-substituted 3-amino-5-trifluoromethanesulfonyloxy-3,4-dihydro-2H-1-benzopyran.

PET-Determination of robalzotan (NAD-299) induced 5-HT(1A) receptor occupancy in the monkey brain.

The serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor subtype is of central interest in research, particularly in the area of pathophysiology and pharmacological treatment of psychiatric disorders. Robalzotan (generic name for NAD-299) is a new putative drug that binds with high selectivity and affinity to 5-HT(1A)-receptors in the rodent brain in vitro and in vivo. The aim of this positron emission tomography study was to determine 5-HT(1A) receptor occupancy in the cynomolgus monkey brain in vivo after IV injection of robalzotan.