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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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. Two healthy monkeys were examined with Positron Emission Tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635, the first after IV administration of 2 microg/kg and 20 microg/kg, and the second after 10 microg/kg and 100 microg/kg IV. 5-HT(1A) receptor occupancy was calculated using an equilibrium-ratio analysis. Robalzotan occupied 5-HT(1A) receptors in a dose-dependent and saturable manner. The highest 5-HT(1A) receptor occupancy (70-80%) was attained after 100 microg/kg. The relationship between robalzotan drug concentration and 5-HT(1A) receptor occupancy could be described by a hyperbolic function, which can be used to guide the selection of appropriate doses for the initial studies in man. The study further corroborates that quantitative neuroimaging of receptor binding has potentials for the evaluation and dose finding of new CNS drugs.[1]


  1. PET-Determination of robalzotan (NAD-299) induced 5-HT(1A) receptor occupancy in the monkey brain. Farde, L., Andrée, B., Ginovart, N., Halldin, C., Thorberg, S. Neuropsychopharmacology (2000) [Pubmed]
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