Capsazepine is a synthetic
antagonist of
capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burnin ...
.
It is used as a biochemical tool in the study of
TRPV
TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective.
TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasm ...
ion channels.
Pharmacology
Capsazepine blocks the painful sensation of heat caused by capsaicin (the active ingredient of
chilli pepper
Chili peppers (also chile, chile pepper, chilli pepper, or chilli), from Nahuatl '' chīlli'' (), are varieties of the berry-fruit of plants from the genus ''Capsicum'', which are members of the nightshade family Solanaceae, cultivated for t ...
) which activates the
TRPV1
The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...
ion channel. Capsazepine is therefore considered to be a TRPV1
antagonist. The TRPV1 channel functions as a pain and temperature sensor in
mammalians. Capsazepine blocks the activation of TRPV1 channels by other chemicals, but not by other painful stimuli such as heat. Depending on the pharmacological assay, the
IC50 is in the
nanomolar
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...
to low
micromolar
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of sol ...
range. In addition to its effects on TRPV1 channels, it was also shown to activate the noxious chemical sensor
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
channel,
inhibit the cold activated
TRPM8
Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...
channel,
and
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s.
It mainly serves as a tool to study the TRPV1 ion channel.
Development
Capsazepine was discovered by a research group working for
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
.
[ Its synthesis and chemical properties were published in 1994. It was found by modification of the chemical backbone of capsaicin.]
Use in biotechnology
By incorporation of an azobenzene
Azobenzene is a photoswitchable chemical compound composed of two phenyl rings linked by a N=N double bond. It is the simplest example of an aryl azo compound. The term 'azobenzene' or simply 'azo' is often used to refer to a wide class of simi ...
unit, a photoswitchable version of capsazepine (AC4) was developed in 2013 that allows for optical control of TRPV1
The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...
channels with light.
LMU Munich, 07/25/2013
See also
*
Discovery and development of TRPV1 antagonists
*
Menthol
*
Herkinorin
*
JWH-133
References
{{Transient receptor potential channel modulators
Capsaicinoids
Catechols
Benzazepines
Chlorobenzenes
Thioureas