Harman

Bioactive beta-carbolines norharman and harman in traditional and novel raw materials for chicory coffee.[Pubmed:25577081]

Food Chem. 2015 May 15;175:280-3.

The beta-carboline compounds norHarman and Harman exhibit neuroactive activity in the human body. Chicory coffee has proved to be a source of beta-carboline compounds. This study assessed the norHarman and Harman contents of traditional and novel raw materials for the production of chicory coffee, as well as in samples of chicory coffee with novel additives. The highest content of the beta-carbolines among the traditional raw materials was recorded in roasted sugar beet (2.26 mug/g), while roasting the chicory caused a 25-fold increase in the content of norHarman in this raw material (from 0.05 to 1.25 mug/g). In novel raw materials not subjected to the action of high temperature, beta-carboline was not detected. Among the roasted novel raw materials, the highest contents of Harman and norHarman were found in artichokes. High Harman levels were also recorded in roasted chokeberry.

Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors.[Pubmed:10725251]

Br J Pharmacol. 2000 Mar;129(6):1057-9.

The beta-carboline, Harmane (0.1 - 1.0 nmol) produces dose dependent hypotension when microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of the anaesthetized rat. The potency of Harmane on blood pressure is similar to that of the imidazoline, clonidine. The hypotensive effects of both clonidine and Harmane are reversed by microinjection of the relatively I(1)-receptor selective antagonist efaroxan (20 nmol). These results are consistent with Harmane acting at an I(1)-receptor in the RVLM. This is the first report of an endogenous ligand for I(1)-receptors that has central effects on blood pressure.

The I1-imidazoline receptor and its cellular signaling pathways.[Pubmed:10415895]

Ann N Y Acad Sci. 1999 Jun 21;881:35-53.

Two primary questions are addressed. First, do I1-imidazoline binding sites fulfill all the essential criteria for identification as a true receptor? Second, what are the cellular signaling pathways coupled to this novel receptor? I1-imidazoline binding sites show specificity in binding assays, linkage to physiologic functions, appropriate anatomic, and cellular and subcellular localization. Most important, binding affinities correlate with functional drug responses. I1-imidazoline binding sites meet several additional criteria identified with functional receptors: they show physiologic regulation and endogenous ligands and, most crucially, are coupled to cellular signaling events. A series of studies have identified cellular events triggered by I1-imidazoline receptor occupancy. This receptor is not coupled to conventional pathways downstream of heterotrimeric G-proteins, such as activation or inhibition of adenylyl or guanylyl cyclases, stimulation of inositol phospholipid hydrolysis, or induction of rapid calcium fluxes. The I1-imidazoline receptor is coupled to choline phospholipid hydrolysis, leading to the generation of diacylglyceride, arachidonic acid, and eicosanoids. Additional cellular responses include inhibition of Na+/H+ exchange and induction of genes for catecholamine synthetic enzymes. The signaling pathways linked to the I1-imidazoline receptor are similar to those of the interleukin family, implying that I1-receptors may belong to the family of neurocytokine receptors.

beta-Carbolines as selective monoamine oxidase inhibitors: in vivo implications.[Pubmed:7130973]

J Neural Transm. 1982;54(3-4):209-18.

The inhibitory action of a range of beta-carbolines on human and rat monoamine oxidase (MAO) A and B has been studied. Concentrations of 5-hydroxytryptamine and phenylethylamine, approximately at their Km values, were used as substrates for MAO A and B respectively. A wide variation in selectivity was found, with harmaline being 10,000 times more potent an inhibitor of A than B whereas, using tetrahydro-beta-carboline and Harmane, the difference was nearer to ten-fold. Of the carbolines which have been found endogenously, tetrahydro-beta-carboline, 6-methoxytetrahydro-beta-carboline and Harmane are all sufficiently potent inhibitors of human MAO A, with I50 values of 5 X 10(-6), 10(-6), 5 X 10(-7) M respectively, for this property to be of possible physiological significance. Harmane, with an I50 of 5 X 10(-6) M, might also play a role as an inhibitor of MAO B.