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| Formula | C18H12Cl2FN5O3S2 |
| Molar mass | 500.34 g·mol−1 |
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PF-05089771 is a selective, small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker under development by Pfizer as a novel analgesic. [1] [2] [3] As of June 2014, it has completed phase II clinical trials for wisdom tooth removal and primary erythromelalgia. [4]
Congenital insensitivity to pain (CIP), also known as congenital analgesia, is one or more extraordinarily rare conditions in which a person cannot feel physical pain. The conditions described here are separate from the HSAN group of disorders, which have more specific signs and cause. Because feeling physical pain is vital for survival, CIP is an extremely dangerous condition. It is common for people with the condition to die in childhood due to injuries or illnesses going unnoticed. Burn injuries are among the more common injuries.
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels.
Nav1.7 is a sodium ion channel that in humans is encoded by the SCN9A gene. It is usually expressed at high levels in two types of neurons: the nociceptive (pain) neurons at dorsal root ganglion (DRG) and trigeminal ganglion and sympathetic ganglion neurons, which are part of the autonomic (involuntary) nervous system.
Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel protein which is encoded by the SCN11A gene on chromosome 3 in humans. Like Nav1.7 and Nav1.8, Nav1.9 plays a role in pain perception. This channel is largely expressed in small-diameter nociceptors of the dorsal root ganglion and trigeminal ganglion neurons, but is also found in intrinsic myenteric neurons.
Nav1.8 is a sodium ion channel subtype that in humans is encoded by the SCN10A gene.
Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels.
The hot plate test is a test of the pain response in animals, similar to the tail flick test. Both hot plate and tail-flick methods are used generally for centrally acting analgesic, while peripherally acting drugs are ineffective in these tests but sensitive to acetic acid-induced writhing test.
Funapide (INN) is a novel analgesic under development by Xenon Pharmaceuticals for the treatment of a variety of chronic pain conditions, including osteoarthritis, neuropathic pain, postherpetic neuralgia, and erythromelalgia, as well as dental pain. It acts as a small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker. Funapide is being evaluated in humans in both oral and topical formulations, and as of July 2014, has reached phase IIb clinical trials.
Vixotrigine, formerly known as raxatrigine, is an analgesic which is under development by Convergence Pharmaceuticals for the treatment of lumbosacral radiculopathy (sciatica) and trigeminal neuralgia (TGN). Vixotrigine was originally claimed to be a selective central Nav1.3 blocker, but was subsequently redefined as a selective peripheral Nav1.7 blocker. Following this, vixotrigine was redefined once again, as a non-selective voltage-gated sodium channel blocker. As of January 2018, it is in phase III clinical trials for trigeminal neuralgia and is in phase II clinical studies for erythromelalgia and neuropathic pain. It was previously under investigation for the treatment of bipolar disorder, but development for this indication was discontinued.
DSP-2230 is a selective small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker which is under development by Dainippon Sumitomo Pharma for the treatment of neuropathic pain. As of June 2014, it is in phase I/phase II clinical trials.
Voltage-gated sodium channels (VGSCs), also known as voltage-dependent sodium channels (VDSCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the sodium ion Na+. They are the main channels involved in action potential of excitable cells.
Ssm6a, or μ-SLPTX-Ssm6a, is a toxin from the venom of the Chinese red-headed centipede. It has strong analgesic properties, probably owing to its strong inhibitory effects on Nav1.7 channels.
Leconotide is an ω-conotoxin peptide isolated from the venom of Conus catus which is under investigation as an analgesic drug for the treatment of pain conditions.
Stephen George Waxman is an American neurologist and neuroscientist. He served as Chairman of the Department of Neurology at Yale School of Medicine, and Neurologist-in-Chief at Yale-New Haven Hospital from 1986 until 2009. As of 2023, he is the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University. He founded the Yale University Neuroscience & Regeneration Research Center in 1988 and is its Director. He previously held faculty positions at Harvard Medical School, MIT, and Stanford Medical School. He is also visiting professor at University College London. He is the editor-in-chief of The Neuroscientist.
Protoxin-II, also known as ProTx-II, PT-II or β/ω-TRTX-Tp2a, is a neurotoxin that inhibits certain voltage-gated calcium and voltage-gated sodium channels. This toxin is a 30-residue disulfide-rich peptide that has unusually high affinity and selectivity toward the human Nav1.7. channel.
N58A is a peptide depressant β-neurotoxin found in the venom of certain East Asian scorpions. The toxin affects voltage-gated sodium channels, specifically Nav1.8 & Nav1.9 channels.
Protoxin-I, also known as ProTx-I, or Beta/omega-theraphotoxin-Tp1a, is a 35-amino-acid peptide neurotoxin extracted from the venom of the tarantula Thrixopelma pruriens. Protoxin-I belongs to the inhibitory cystine knot (ICK) family of peptide toxins, which have been known to potently inhibit voltage-gated ion channels. Protoxin-I selectively blocks low voltage threshold T-type calcium channels, voltage gated sodium channels and the nociceptor cation channel TRPA1. Due to its unique ability to bind to TRPA1, Protoxin-I has been implicated as a valuable pharmacological reagent with potential applications in clinical contexts with regards to pain and inflammation
Phlotoxin is a neurotoxin from the venom of the tarantula Phlogiellus that targets mostly voltage-sensitive sodium channels and mainly Nav1.7. The only non-sodium voltage-sensitive channel that is inhibited by Phlotoxin is Kv3.4. Nav1.4 and Nav1.6 seem to be Phlotoxin-1-sensitive to some extent as well.
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