The beta-carbolines (harmanes) - a new class of endogenous compounds: their relevance for the pathogenesis and treatment of psychiatric and neurological diseases.

Abstract

Research in neurochemistry is occupied with attempting to discover the mechanisms of the transfer of information by neurotransmitters in the central nervous system (CNS). In this context certain derivatives of the biogenic amines have come under increased scrutiny. Especially their relevance for pathological processes plays a major role in this discussion. In principle such derivatives may elicit or exacerbate abnormal reactions. On the other hand they may act as protective substances. The present review deals mainly with the β-carbolines which are derivatives of indolealkylamines (e.g. serotonin, tryptamine). These substances can be found in several organs of humans and animals. Their possible significance for schizophrenic psychoses, depressive illnesses, behavioural changes following alcohol consumption and withdrawal delirium as well as for Morbus Parkinson is discussed. Furthermore, findings are presented about their interference with the benzodiazepine binding site. Compared with the phenothiazines the β-carbolines display similar effects with respect to motor activity. They induce hypokinesia and tremor. Like reserpine, they block the transport of biogenic amines into the synaptic vesicles. In experimental clinical studies it was found that β-carbolines induce autistic tendencies. Furthermore, hallucinations, mostly visual ones which are usually not mistaken for reality, euphoric mood changes, and aggressive behaviour are reported. Compared with the thymoleptics, the β-carbolines act in a similar manner as they react agonistically to serotonin at the synaptic level. The concentration of certain β-carbolines is increased following ingestion of ethanol. The convulsions in the course of chronic alcoholism and withdrawal may be correlated with a β-carboline (harmane) which lowers the threshold for seizures. In humans a similarity of the effects of β-carbolines to some symptoms of ethanol intoxication and delirium tremens can be demonstrated. β-carbolines display a high affinity towards the benzodiazepine binding site on neuronal membranes. There is now good evidence for β-carbolines as endogenous ligands at the benzodiazepine binding site. A correlation exists between the convulsive potency of β-carbolines and their affinity to the benzodiazepine binding site. Thus, β-carbolines act in an antagonistic manner to the benzodiazepines. In conclusion, the β-carbolines can be regarded as a group of compounds with a broad spectrum of activity differing from substance to substance. Their significance for physiological and pathological processes can be elaborated only by investigating the effects of individual compounds. This is of particular importance in the discussion of subtile psychic changes. Using this approach may permit us to answer the question as to whether they play a protective or pathogenic role, or both.