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

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
Why are the terpenoid indole alkaloids of type I homochiral?	2001 Aug	11466772
Genotoxic effects of the alkaloids harman and harmine assessed by comet assay and chromosome aberration test in mammalian cells in vitro.	2001 Dec	11903953
Degradation of tetrahydro-beta-carbolines in the presence of nitrite: HPLC-MS analysis of the reaction products.	2001 Dec	11743798
Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats.	2001 Dec 21	11766171
Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats.	2001 Feb 26	11165749
Anti-AIDS agents. 46. Anti-HIV activity of harman, an anti-HIV principle from Symplocos setchuensis, and its derivatives.	2001 Jul	11473435
Tryptophan: a precursor for the endogenous synthesis of norharman in man.	2001 May 11	11323106
beta-carboline binding to imidazoline receptors.	2001 Oct 1	11543990
Tetrahydro-beta-carboline alkaloids that occur in foods and biological systems act as radical scavengers and antioxidants in the ABTS assay.	2002 Aug	12420751
Elevation of blood beta-carboline alkaloids in essential tremor.	2002 Dec 24	12499487
Synergistic in vitro antimalarial activity of plant extracts used as traditional herbal remedies in Mali.	2002 Feb	11936507
Identification and occurrence of the novel alkaloid pentahydroxypentyl-tetrahydro-beta-carboline-3-carboxylic acid as a tryptophan glycoconjugate in fruit juices and jams.	2002 Jul 31	12137498
An in vitro study on the kinetics, subcellular distribution and phototoxicity of harmine in human tumor cells.	2002 Mar-Apr	12135165
Interaction of folk medicinal plant extracts with human alpha2-adrenoceptor subtypes.	2002 Mar-Apr	12064736
Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca.	2002 Nov 5	12361741
Structure of DNA adduct formed with aminophenylnorharman, being responsible for the comutagenic action of norharman with aniline.	2002 Oct	12387627
Contribution of the alpha1-GABA(A) receptor subtype to the pharmacological actions of benzodiazepine site inverse agonists.	2002 Sep	12367613
Craving for cigarettes among low and high dependent smokers: impact of norharman.	2003 Dec	14690883
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
Long-term retention of neurotoxic beta-carbolines in brain neuromelanin.	2004 Feb	14767717
Cytotoxic alkaloids from the marine sponge Thorectandra sp.	2004 Jun	15143832
Mutagens formed from beta-carbolines with aromatic amines.	2004 Mar 25	15036005
Exposure to beta-carbolines norharman and harman.	2004 Mar 25	15036003
Photophysics of norharmane in micellar environments: a fluorometric study.	2004 May 1	15110944

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.

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