[11C]NS2381

Serotonin is a key neurotransmitter in a variety of neuropsychiatric disorders.It is therefore of interest to determine the functional status of serotonergic processes in the living brain.We have carried out positron emission tomog. (PET) research on two strategies for doing so, namely the fenfluramine activation test and the pharmacokinetics of antidepressant drugs.We used fenfluramine and obtained quant. measurements of the effects of serotonergic stimulation on regional cerebral blood flow (rCBF) and on regional cerebral metabolism of glucose and oxygen (rCMR_glc and rCMR_O2).Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR_O2, but it failed to affect rCMR_glc.The findings indicate that repeated quant. estimation of rCBF was more sensitive than either rCMR_O2 or rCMR_glc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.Next, we used new selective serotonin reuptake inhibitors, NS2381 and its enantiomers, radiolabeled with ¹¹C, for quantifying the serotonin uptake site in the living brain.[¹¹C]NS2381 accumulated readily in brain and bonded reversibly in regions rich in serotonin uptake sites.In addition, [¹¹C]NS2381 was displaced from brain tissue by citalopram, a potent inhibitor of serotonin uptake.However, [¹¹C]NS2381 has a relatively high degree of nonspecific binding in brain regions, and the enantiomers of [¹¹C]NS2381 were, in general, similar to the racemate in terms of their uptake and distribution in living pig brain.Consequently, the search goes on for an ideal positron emission tomog. radioligand for quantifying serotonin reuptake in the living brain.(c) 2001 Academic Press.