Demonstration of a distinct class of high-affinity binding sites for [3H]norharman [( 3H]beta-carboline) in the rat...

Specific binding sites were demonstrated for some beta-carbolines in the rat brain with [3H]norharman as a ligand. The ligand displayed a high affinity for synaptosomal membranes which had been fractionated by a sucrose gradient. The calculated apparent KD value was 1.55 nmol/l and the maximum number of binding sites 148 fmol/mg protein. Displacement studies showed an exclusive specificity for a small group of beta-carbolines but not for the previously described inverse agonists at the benzodiazepine receptor nor for tryptamine and other indoles, as well as pargyline, a monoamine oxidase inhibitor. Further analysis revealed other binding sites for [3H]norharman, with an apparent KD value of 36 nmol/l that are presumably located on mitochondrial membranes. Binding to these sites was also not displaced by pargyline. Pargyline displaced [3H]norharman from a third population of binding sites on mitochondrial membranes with the apparent KD value of 46 nmol/l. These findings could explain the pharmacological effects of norharman and other beta-carbolines in vivo.