β‐CARBOLINES: A TOOL FOR INVESTIGATING STRUCTURE‐ACTIVITY RELATIONSHIPS OF THE HIGH‐AFFINITY UPTAKE OF SEROTONIN, NORADRENALINE, DOPAMINE, GABA AND CHOLINE INTO A SYNAPTOSOME‐RICH FRACTION OF VARIOUS REGIONS FROM RAT BRAIN1

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Abstract
Abstract— Tetrahydronorharmane (tryptoline), the condensation product of tryptamine and formaldehyde, inhibits the high‐affinity uptake of serotonin and to a smaller extent that of noradrenaline into a synaptosome‐rich fraction from the hippocampus and hypothalamus respectively of rats. The uptake mechanisms of dopaminergic neurones of the hypothalamus, cholinergic neurones of the hippocampus, and GABA‐ergic neurones of the cerebral cortex are affected to a much lesser degree. Substitution of tetrahydronorharmane by fluor‐, chlor‐, methyl‐, hydroxy‐, methoxy‐, and catechol‐groups alters the inhibition. Drugs with substituents which attract electrons are relatively good inhibitors of the uptake of serotonin. The indole‐ring contributes to the binding of the molecule probably by forming a charge transfer complex with the uptake molecule. Pyrido (3,4‐b)‐indoles (harmala alkaloids) are weak inhibitors of the serotonin‐uptake compared with respective piperidoindoles (tetrahydro‐β‐carbolines).The potency of the drugs to inhibit uptake is different for each uptake system. The order among the drugs with respect to their affinity for the uptake site varies, too.

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