7-Nitroindazole
Encyclopedia
7-Nitroindazole, or 7-NI, is a heterocyclic
small molecule
containing an indazole
ring that has been nitrated
at the 7 position. Nitroindazole acts as a selective inhibitor for neuron
al nitric oxide synthase
, a hemoprotein enzyme
that, in neuron
al tissue, converts arginine
to citrulline
and nitric oxide
(NO). Nitric oxide can diffuse through the plasma membrane into neighbouring cells, allowing cell signalling, so nitroindazole indirectly inhibits this signalling process. Other inhibitors exist such as 3-bromo-7-nitroindazole, which is more potent but less specific, or NPA (N-propyl-L-arginine
), which acts on a different site.
caused by excitotoxicity
or neurodegenerative diseases. It may act by reducing oxidative stress
or by decreasing the amount of peroxynitrite
formed in these tissues.
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
small molecule
Small molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...
containing an indazole
Indazole
Indazole, also called benzpyrazole or isoindazone, is a heterocyclic aromatic organic compound.Indazole derivatives display a broad variety of biological activities....
ring that has been nitrated
Nitration
Nitration is a general chemical process for the introduction of a nitro group into a chemical compound. The dominant application of nitration is for the production of nitrobenzene, the precursor to methylene diphenyl diisocyanate...
at the 7 position. Nitroindazole acts as a selective inhibitor for neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al nitric oxide synthase
Nitric oxide synthase
Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...
, a hemoprotein enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that, in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al tissue, converts arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
to citrulline
Citrulline
The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated in 1930.It has the idealized formula H2NCNH3CHCO2H...
and nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(NO). Nitric oxide can diffuse through the plasma membrane into neighbouring cells, allowing cell signalling, so nitroindazole indirectly inhibits this signalling process. Other inhibitors exist such as 3-bromo-7-nitroindazole, which is more potent but less specific, or NPA (N-propyl-L-arginine
N-propyl-L-arginine
N-Propyl-L-arginine, or more properly NG-propyl-L-arginine , is a selective inhibitor of neuronal nitric oxide synthase ....
), which acts on a different site.
Pharmacology
7-Nitroindazole is under investigation as a possible protective agent against nerve damageNerve Damage
Nerve Damage is a compilation album by Groove Metal band Skinlab, released in 2004. It is a 2CD collection of rare and unreleased material, including a live set, demos, remixes, alternate mixes, and two new tracks.-Disc 1:# "Losing All" – 4:04...
caused by excitotoxicity
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
or neurodegenerative diseases. It may act by reducing oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
or by decreasing the amount of peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...
formed in these tissues.
See also
- DizocilpineDizocilpineDizocilpine , also known as MK-801, is a non-competitive antagonist of the N-methyl-d-aspartate receptor, a glutamate receptor. Glutamate is the brain's primary excitatory neurotransmitter...
(MK-801) a non-competitive antagonist of the NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function.... - SildenafilSildenafilSildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
a drug for impotence, which inhibits cGMP specific phosphodiesterase type 5CGMP specific phosphodiesterase type 5cGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina....
(PDE5), which is responsible for degradation of cGMPCyclic guanosine monophosphateCyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...
, which is produced by guanylate cyclase, which is activated by nitric oxide produced by eNOS - tetrahydrobiopterinTetrahydrobiopterinTetrahydrobiopterin or sapropterin is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin , melatonin, dopamine, norepinephrine ,...
, cofactor to several enzymes including nitric oxide synthase (NOS) - protein kinase A (PKA) and protein kinase CProtein kinase CProtein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
(PKC)