An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.
Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.
Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).
Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge, a cactus-like plant commonly found in Morocco, and in Euphorbia poissonii found in northern Nigeria. It is a potent functional analog of capsaicin, the active ingredient in chili peppers.
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 the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA). The function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 to mediate the detection of noxious environmental stimuli.
TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.
Nonivamide, also called pelargonic acid vanillylamide or PAVA, is an organic compound and a capsaicinoid. It is an amide of pelargonic acid and vanillyl amine. It is present in chili peppers, but is commonly manufactured synthetically. It is more heat-stable than capsaicin.
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 gene.
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 transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.
N-Arachidonoyl dopamine (NADA) is an endocannabinoid that acts as an agonist of the CB1 receptor and the transient receptor potential V1 (TRPV1) ion channel. NADA was first described as a putative endocannabinoid (agonist for the CB1 receptor) in 2000 and was subsequently identified as an endovanilloid (agonist for TRPV1) in 2002. NADA is an endogenous arachidonic acid based lipid found in the brain of rats, with especially high concentrations in the hippocampus, cerebellum, and striatum. It activates the TRPV1 channel with an EC50 of approximately of 50 nM which makes it the putative endogenous TRPV1 agonist.
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].
Iodoresiniferatoxin (I-RTX) is a strong competitive antagonist of the Transient Receptor Potential Vanilloid 1 (TRPV1) receptor. I-RTX is derived from resiniferatoxin (RTX).
Relief from chronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is a ligand gated ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively. The first competitive antagonist, capsazepine, was first described in 1990; since then, several TRPV1 antagonists have entered clinical trials as analgesic agents. Should these new chemical entities relieve symptoms of chronic pain, then this class of compounds may offer one of the first novel mechanisms for the treatment of pain in many years.
Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.
LASSBio-881 is a drug which acts as both a non-selective partial agonist of the CB1 and CB2 cannabinoid receptors, and also as an antagonist of the TRPV1 receptor, as well as having antioxidant effects. It has potent anti-inflammatory and anti-hyperalgesic effects in animal studies.
The 25-NB (25x-NBx) series, sometimes alternatively referred to as the NBOMe compounds, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. They act as selective agonists of the serotonin 5-HT2A receptor. The 25-NB family is unique relative to other classes of psychedelics in that they are, generally speaking, extremely potent and relatively selective for the 5-HT2A receptor. Use of NBOMe series drugs has caused many deaths and hospitalisations since the drugs popularisation in the 2010s. This is primarily due to their high potency, unpredictable pharmacokinetics, and sellers passing off the compounds in the series as LSD.
AMG-9810 is a drug which acts as a potent and selective antagonist for the TRPV1 receptor. It has analgesic and antiinflammatory effects and is used in scientific research, but has not been developed for medical use. It has high antagonist potency and good bioavailability and pharmacokinetics, and so has been used to study the role of TRPV1 in areas other than pain perception, such as its roles in the brain.
SB-705498 is a drug which acts as a potent and selective blocker of the TRPV1 ion channel. It has been evaluated in clinical trials for the treatment of rhinitis and chronic cough.
Double-knot toxin (DkTx), also known as Tau-theraphotoxin-Hs1a or Tau-TRTX-Hs1a, is a toxin found in the venom of the Chinese Bird spider, a tarantula species primarily living in the Guangxi province of China. This toxin, characterized by its bivalent structure of two Inhibitor Cysteine Knots (ICK), is thought to induce excruciating and long-lasting pain by activating the transient receptor potential vanilloid 1 (TRPV1) channel.
