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 nervous system, muscle, and many other tissues of many organisms. At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. In the immune system, nAChRs regulate inflammatory processes and signal through distinct intracellular pathways. In insects, the cholinergic system is limited to the central nervous system.
Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.
A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.
The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor implicated in learning, consisting of α4 and β2 subunits. It is located in the brain, where activation yields post- and presynaptic excitation, mainly by increased Na+ and K+ permeability.
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].
Cholinergic receptor, nicotinic, alpha 6, also known as nAChRα6, is a protein that in humans is encoded by the CHRNA6 gene. The CHRNA6 gene codes for the α6 nicotinic receptor subunit that is found in certain types of nicotinic acetylcholine receptors found primarily in the brain. Neural nicotinic acetylcholine receptors containing α6 subunits are expressed on dopamine-releasing neurons in the midbrain, and dopamine release following activation of these neurons is thought to be involved in the addictive properties of nicotine. Due to their selective localisation on dopaminergic neurons, α6-containing nACh receptors have also been suggested as a possible therapeutic target for the treatment of Parkinson's disease. In addition to nicotine, research in animals has implicated alpha-6-containing nAChRs in the abusive and addictive properties of ethanol, with mecamylamine demonstrating a potent ability to block these properties.
Ispronicline is an experimental drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease, but is no longer under development.
Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stronger than morphine as an analgesic, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound. It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes.
GTS-21 (DMXBA) is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent.
Pozanicline is a drug developed by Abbott, that has nootropic and neuroprotective effects. Animal studies suggested it useful for the treatment of ADHD and subsequent human trials have shown ABT-089 to be effective for this application. It binds with high affinity subtype-selective to the α4β2 nicotinic acetylcholine receptors and has partial agonism to the α6β2 subtype, but not the α7 and α3β4 subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class, making it an exciting candidate for clinical development.
UB-165 is a drug which acts as an agonist at neuronal nicotinic acetylcholine receptors being a full agonist of the α3β2 isoform and a partial agonist of the α4β2* isoform. It is used to study the role of this receptor subtype in the release of dopamine and noradrenaline in the brain, and has also been used as a lead compound to derive a number of other selective nicotinic receptor ligands.
Altinicline is a drug which acts as an agonist at neural nicotinic acetylcholine receptors with high selectivity for the α4β2 subtype. It stimulates release of dopamine and acetylcholine in the brain in both rodent and primate models, and progressed as far as Phase II clinical trials for Parkinson's disease, where "no antiparkinsonian or cognitive-enhancing effects were demonstrated", although its current status is unclear.
PNU-282,987 is a drug that acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors. In animal studies, it shows nootropic effects, and derivatives may be useful in the treatment of schizophrenia, although PNU-282,987 is not suitable for use in humans because of excessive inhibition of the hERG antitarget. PNU-282987 has been shown to initiate signaling that leads to adult neurogeneis in mammals.
SSR180711 is a drug that acts as a potent and selective partial agonist for the α7 subtype of neural nicotinic acetylcholine receptors. In animal studies, it shows nootropic effects and may be useful in the treatment of schizophrenia.
The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability.
WAY-317538 (SEN-12333) is a drug that acts as a potent and selective full agonist for the α7 subtype of neural nicotinic acetylcholine receptors. It was not the most potent compound in the series, but was selected for further development on the basis of its high selectivity over related receptors, ease of synthesis, and good in vivo properties including high oral bioavailability and good brain penetration. It has nootropic and neuroprotective effects in animal studies, and is being investigated as a potential treatment for neurodegenerative and neurocognitive conditions including Alzheimer's disease and schizophrenia.
Nitromemantine is a derivative of memantine developed in 2006 for the treatment of Alzheimer's disease. It has been shown to reduce excitotoxicity mediated by over-activation of the glutamatergic system, by blocking NMDA receptors.
The alpha-3 beta-2 nicotinic receptor, also known as the α3β2 receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β2 subunits.
Anabaseine (3,4,5,6-tetrahydro-2,3′-bipyridine) is an alkaloid toxin produced by Nemertines and Aphaenogaster ants. It is structurally similar to nicotine and anabasine. Similarly, it has been shown to act as an agonist on most nicotinic acetylcholine receptors in the central nervous system and peripheral nervous system.
The alpha-5 nicotinic acetylcholine receptor(α5 nAChR) also known as the α5 receptor is a type of ligand gated nicotinic acetylcholine receptor involved in pain regulation. One of the 5 transmembrane subunits of this receptor is the α5 subunit and is transcribed by the CHRNA5 gene. This receptor is commonly associated with nicotine addiction, immunotherapy, cancer, pain and attention.
