Carbon 11 labeling of the psychoactive drug o-methyl-bufotenine and its distribution in the animal organism.

O-methyl-bufotenine, a serotonin derivative, can be produced in high purity and quantity using a novel methylation method, yielding several tens of millicuries in just 50 minutes. This compound exhibits a specific radioactivity of 50 to 100 mCi/mumol. In distribution studies involving mice and rabbits, significant accumulation was observed in the brain (notably), kidneys, lungs, and liver. Its rapid kinetics, with a 20-minute half-life, makes O-methyl-[11C]bufotenine a promising tool for in vivo detection of serotonin receptors related to mental health conditions.

Study at a glance

Abstract

A methylated derivative of serotonin, O-methyl-bufotenine has been labeled with 11C on the two methyl groups of the amine function. In order to avoid the cyclization which occurs during the Eschweiler-Clarke synthesis, we adopted a milder methylation procedure, based on Borch's method using [11C]formaldehyde and sodium cyanoborohydride. Several tens of millicuries of injectable product could be obtained in 50 min in a perfectly pure state and having a specific radioactivity of 50 to 100 mCi/mumol. The distribution study of O-methyl-bufotenine in the mouse and rabbit showed an accumulation of significant quantities of the compound in the brain, kidneys, lungs and liver. The study of the rapid kinetics of this hallucinogenic molecule is compatible with labeling by 11C, having a period of 20 min. The use of O-methyl-[11C]bufotenine to detect serotonin receptors in vivo in mental diseases, is considered.