β-Carbolines and Tetrahydroisoquinolines: Detection and Function in Mammals

Abstract

beta-Carbolines occur in man and rat. The concentration in various tissues is about 100 to 1000 times lower than that of classical neurotransmitters. Administration of beta-carbolines in animals induces overlapping but not identical activity profiles. The molecular modes of action differ. For example, harman (1-methyl-beta-carboline) acts as an endogenous inhibitor of monoamine oxidase [E.C. 1.4.3.4.], subtype A, whereas norharman (beta-carboline) probably acts by stimulation of a specific beta-carboline receptor which is different from the benzodiazepine-GABA receptor complex. There is substantial evidence that tetrahydroisoquinolines occur under physiological conditions as well. Whether tetrahydropapaveroline serves as a precursor of morphinanes in mammals, as has been found in opium poppies, remains to be elucidated.

Elevated levels of harman and norharman in cerebrospinal fluid of Parkinsonian patients

“…Biochemically norharman acts as a natural endogenous sedative but not hallucinatory agent in a certain range of concentration (Fekkes et al, 1992;Fekkes and Bode, 1993). Moreover norharman may stimulate a specific betacarboline receptor, different from the benzodiazepine-GABA receptor complex (Pawlik et al, 1990;Rommelspacher et al, 1991a). In the case of harman it has been demonstrated, that this substance is a strong endogenous inhibitor of monoaminooxidase A (MAO-A) in contrast to norharman.…”

Exposure to β-carbolines norharman and harman

“…Rommelspacher et al [77] investigated the endogenous formation of harman in mammals. Using 3 H-labelled compounds, tryptamine was identified as a precursor which condensates with pyruvate to 1,2,3,4-tetrahydro-1-methyl-␤-carboline-1-carboxylic acid.…”

Cyclic azomethines and their hydrogenated derivatives. (Review)

“…The role of 1,2,3,4-tetrahydroisoquinoline in dopaminergic processes is known [275][276][277][278][279][280][281][282][283][284]. Some isoquinoline derivatives, more complex in structure, such as 100 [285] and 101 [286], are known as psychotropic dopamine antagonists. Derivatives of 1,2,3,4-tetrahydroisoquinoline with no substituent at position 1 may be monoamine oxidase inhibitors [287][288][289], and also display a different action in relation to adrenoreceptors [290][291][292][293].…”