NORHARMAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H8N2
Molecular Weight	168.1946
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N1C2=CC=CC=C2C3=C1C=NC=C3

InChI

InChIKey=AIFRHYZBTHREPW-UHFFFAOYSA-N

InChI=1S/C11H8N2/c1-2-4-10-8(3-1)9-5-6-12-7-11(9)13-10/h1-7,13H

HIDE SMILES / InChI

Molecular Formula	C11H8N2
Molecular Weight	168.1946
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.sciencedirect.com/science/article/pii/B9780124095175000826 | https://www.ncbi.nlm.nih.gov/pubmed/15036003 | https://www.ncbi.nlm.nih.gov/pubmed/15582589 | https://www.ncbi.nlm.nih.gov/pubmed/2789076 | https://www.ncbi.nlm.nih.gov/pubmed/16061219 | https://www.ncbi.nlm.nih.gov/pubmed/1877743 | https://www.ncbi.nlm.nih.gov/pubmed/8750109

Norharman or beta-carboline (9H-pyrido[3,4-b]indole) is a neuroactive alkaloid first isolated from Peganum harmala L. It is implicated in a number of human diseases including Parkinson's disease, tremor, addiction and cancer. Norharman formed endogenously but external sources have been identified (among others fried meat and fish, meat extracts, alcoholic drinks, coffee brews, tobacco smoke). It inhibits monoamine oxidase and indoleamine 2,3-dioxygenase. In addition norharman binds with high affinity to imidazoline I2B receptors. Plasma norharman levels are elevated in chronic alcoholics and Parkinson's disease patients.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Indoleamine 2,3-dioxygenase 19 Target ID: CHEMBL4685 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6431906 \| https://www.ncbi.nlm.nih.gov/pubmed/2789076	Inhibitor 8297	0.12 mM [Ki]
alpha-glucosidase activity 2 Target ID: GO:0090599 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25502825	Inhibitor 8297	0.13 mM [Ki]
Monoamine oxidase A 49 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16139309 \| https://www.ncbi.nlm.nih.gov/pubmed/16061219 \| https://www.ncbi.nlm.nih.gov/pubmed/15582589	Inhibitor 8297	1.2 µM [Ki]
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15582589 \| https://www.ncbi.nlm.nih.gov/pubmed/16139309	Inhibitor 8297	1.12 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16183262	Primary	Preclinical	Unknown Approved Use Unknown
Toxoplasmosis 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23663567	Primary	Basic research	Unknown Approved Use Unknown
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16579793	Primary	Basic research	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8750109	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Alcoholism 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8651457 https://www.ncbi.nlm.nih.gov/pubmed/1877743	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Norharman, an indoleamine-derived beta-carboline, but not Trp-P-2, a gamma-carboline, induces apoptotic cell death in human neuroblastoma SH-SY5Y cells.	2001	11716147
Exposure of a 'witness rat' to one treated with beta-carboline FG 7142 does not increase dopamine turnover in the medial prefrontal cortex of the 'witness rat'.	2001 Apr 20	11290409
Stimulatory effect of harmane and other beta-carbolines on locus coeruleus neurons in anaesthetized rats.	2001 Aug 10	11479022
Genotoxic effects of the alkaloids harman and harmine assessed by comet assay and chromosome aberration test in mammalian cells in vitro.	2001 Dec	11903953
[Synthetic studies of the bioactive natural products by using the thermal electrocyclic reaction of 6 pi electron systems].	2001 Jul	11494596
Oxidative DNA damage by an N-hydroxy metabolite of the mutagenic compound formed from norharman and aniline.	2001 Jul 25	11423346
Structures of mutagens produced by the co-mutagen norharman with o- and m-toluidine isomers.	2001 Jun 27	11516721
Reaction of tryptophan with carbohydrates: identification and quantitative determination of novel beta-carboline alkaloids in food.	2001 May	11368624
Cis- and trans-platinum and palladium complexes: a comparative study review as antitumour agents.	2001 May-Jun	11486616
Pharmacokinetics of the beta-carboline norharman in man.	2001 Sep 21	11669455
Multistep mass spectrometry of heterocyclic amines in a quadrupole ion trap mass analyser.	2002 Aug	12203675
5-hydroxytryptamine-derived alkaloids from two marine sponges of the genus Hyrtios.	2002 Aug	12193025
High-performance liquid chromatographic, capillary electrophoretic and capillary electrophoretic-electrospray ionisation mass spectrometric analysis of selected alkaloid groups.	2002 Aug 16	12219932
Elevation of blood beta-carboline alkaloids in essential tremor.	2002 Dec 24	12499487
Synthesis of beta- and gamma-carbolines by the palladium-catalyzed iminoannulation of alkynes.	2002 Dec 27	12492334
The impact of smoking and drinking on plasma levels of norharman.	2002 Feb	11788242
Beta-carboline-carbohydrate hybrids: molecular design, chemical synthesis and evaluation of novel DNA photocleavers.	2002 Feb 25	11844697
An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its beta-carboline alkaloids.	2002 Jan-Apr	12042115
1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) and related derivatives: chemistry and biochemical effects on catecholamine biosynthesis.	2002 Jul	11983518
Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers.	2002 Jun	12047486
Natural variations of precursors in pig meat affect the yield of heterocyclic amines--effects of RN genotype, feeding regime, and sex.	2002 May 8	11982426
[Serum norharman and harman analysis using high pressure liquid chromatography/mass spectrometry and value of beta-carbolines as blood alcohol markers].	2002 Nov-Dec	12532677
Structure of DNA adduct formed with aminophenylnorharman, being responsible for the comutagenic action of norharman with aniline.	2002 Oct	12387627
In vitro and in vivo formation of aminophenylnorharman from norharman and aniline.	2002 Sep 30	12351144
Potential neurotoxic "agents provocateurs" in Parkinson's disease.	2002 Sep-Oct	12200188
Effect of harmane on mononeuropathic pain in rats.	2003 Dec	15028585
Craving for cigarettes among low and high dependent smokers: impact of norharman.	2003 Dec	14690883
Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from isolated human islets of Langerhans.	2003 Dec 15	14660022
Mechanism-based pharmacokinetic/pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in vitro-in vivo correlations.	2003 Jan	12490579
Isolation and identification of two [(3)H]norharman- ([(3)H]beta-carboline)-binding proteins from rat liver.	2003 Jan 25	12504194
Spectrofluorimetric determination of manzamine A in spiked human urine and plasma.	2003 Jun	12856999
Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.	2003 Jun	12777961
Possibility of the involvement of 9H-pyrido[3,4-b]indole (norharman) in carcinogenesis via inhibition of cytochrome P450-related activities and intercalation to DNA.	2003 Nov 10	14568301
Identification of tryptophan and beta-carboline as paralysins in larvae of the yellow mealworm, Tenebrio molitor.	2003 Oct 10	14511649
Long-term retention of neurotoxic beta-carbolines in brain neuromelanin.	2004 Feb	14767717
Cytotoxic alkaloids from the marine sponge Thorectandra sp.	2004 Jun	15143832
Exposure to beta-carbolines norharman and harman.	2004 Mar 25	15036003
Dopamine transporter-mediated cytotoxicity of beta-carbolinium derivatives related to Parkinson's disease: relationship to transporter-dependent uptake.	2004 May	15086525
Photophysics of norharmane in micellar environments: a fluorometric study.	2004 May 1	15110944
Carcinogenicity of aminophenylnorharman, a possible novel endogenous mutagen, formed from norharman and aniline, in F344 rats.	2004 Oct	15142889

Patents

Sample Use Guides

In Vivo Use Guide

Pharmacokinetics of oral norharman in healthy subjects: 7, 65 and 110 microg/kg. Rats: 0.2-20 mg/kg, i.p. Mice: 2.5-10 mg/kg, i.p.

Route of Administration: Other

In Vitro Use Guide

Norharman showed cytotoxicity towards both the HeLa cervical-cancer cell line and the BGC-823 stomach-cancer cell line, with an IC(50) of 5 microg/ml.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:44:11 UTC 2023` Edited by `admin` on `Fri Dec 15 19:44:11 UTC 2023`
Record UNII	94HMA1I78O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NORHARMAN

Common Name

English

NSC-84417

Code

English

CARBAZOLINE

Common Name

English

2,9-DIAZAFLUORENE

Systematic Name

English

.BETA.-CARBOLINE

Systematic Name

English

Code System Code Type Description

MESH

C010262