7-Nitroindazole
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7-Nitroindazole, or 7-NI, is a
heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
small molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ...
containing an
indazole Indazole, also called isoindazole, is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and pyrazole. Indazole is an amphoteric molecule which can be protonated to an indazolium cation or deproton ...
ring that has been nitrated at the 7 position. Nitroindazole acts as a selective inhibitor for
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
al
nitric oxide synthase Nitric oxide synthases () (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and p ...
, a hemoprotein
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that, in
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
al tissue, converts arginine to
citrulline The organic compound citrulline is an α-amino acid. Its name is derived from ''citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1 ...
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.


Pharmacology

7-Nitroindazole is under investigation as a possible protective agent against
nerve damage Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve f ...
caused by
excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate ...
or
neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
s. It may act by reducing
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
or by decreasing the amount of
peroxynitrite Peroxynitrite (sometimes called peroxonitrite) is an ion with the formula ONOO−. It is a structural isomer of nitrate, Preparation Peroxynitrite can be prepared by the reaction of superoxide with nitric oxide: : It is prepared by the react ...
formed in these tissues. These effects are related to the inhibition of type 1 nitric oxide synthase. However, anticonvulsive effect is derived from some other mechanisms.


See also

*
Dizocilpine Dizocilpine (INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is ...
(MK-801) a non-competitive antagonist of the NMDA receptor * Sildenafil a drug for impotence, which inhibits
cGMP specific phosphodiesterase type 5 Cyclic guanosine monophosphate-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. It has also been recently discovered to p ...
(PDE5), which is responsible for degradation of cGMP, which is produced by guanylate cyclase, which is activated by nitric oxide produced by eNOS *
tetrahydrobiopterin Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a 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 ...
, cofactor to several enzymes including nitric oxide synthase (NOS) *
protein kinase A In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...
(PKA) and protein kinase C (PKC)


References


External links

* {{DEFAULTSORT:Nitroindazole, 7- Nitro compounds Oxidoreductase inhibitors Indazoles