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| Names | |
|---|---|
| IUPAC name 4-[(3-Trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider | |
PubChem CID | |
| UNII | |
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| Properties | |
| C14H17F3N3O2+1 | |
| Molar mass | 316.304 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
TDBzcholine is a diazirine analog of acetylcholine that can be used to label the nicotinic acetylcholine receptor.
TDBzcholine is able to bind to the nicotinic acetylcholine receptor. Once TDBzcholine is bound to the receptor, TDBzcholine can be activated by exposing the sample to UV light. This led to formation of a highly reactive carbene radical that can react with amino acid residues in the receptor and become covalently bound to the receptor. [1]
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and cause some form of cellular/tissue response, e.g. a change in the electrical activity of a cell. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway.
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.
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system.
Jean-Pierre Changeux is a French neuroscientist known for his research in several fields of biology, from the structure and function of proteins, to the early development of the nervous system up to cognitive functions. Although being famous in biological sciences for the MWC model, the identification and purification of the nicotinic acetylcholine receptor and the theory of epigenesis by synapse selection are also notable scientific achievements. Changeux is known by the non-scientific public for his ideas regarding the connection between mind and physical brain. As put forth in his book, Conversations on Mind, Matter and Mathematics, Changeux strongly supports the view that the nervous system functions in a projective rather than reactive style and that interaction with the environment, rather than being instructive, results in the selection amongst a diversity of preexisting internal representations.
Hexamethonium is a non-depolarising ganglionic blocker, a nicotinic (nAChR) receptor antagonist that acts in autonomic ganglia by binding mostly in or on the nAChR receptor, and not the acetylcholine binding site itself. It does not have any effect on the muscarinic acetylcholine receptors (mAChR) located on target organs of the parasympathetic nervous system but acts as antagonist at the nicotinic acetylcholine receptors located in sympathetic and parasympathetic ganglia (nAChR).
A muscarinic agonist is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.
A ganglionic blocker is a type of medication that inhibits transmission between preganglionic and postganglionic neurons in the autonomic nervous system, often by acting as a nicotinic receptor antagonist. Nicotinic acetylcholine receptors are found on skeletal muscle, but also within the route of transmission for the parasympathetic and sympathetic nervous system. More specifically, nicotinic receptors are found within the ganglia of the autonomic nervous system, allowing outgoing signals to be transmitted from the presynaptic to the postsynaptic cells. Thus, for example, blocking nicotinic acetylcholine receptors blocks both sympathetic (excitatory) and parasympathetic (calming) stimulation of the heart. The nicotinic antagonist hexamethonium, for example, does this by blocking the transmission of outgoing signals across the autonomic ganglia at the postsynaptic nicotinic acetylcholine receptor.
A nicotinic antagonist is a type of anticholinergic drug that inhibits the action of acetylcholine (ACh) at nicotinic acetylcholine receptors. These compounds are mainly used for peripheral muscle paralysis in surgery, the classical agent of this type being tubocurarine, but some centrally acting compounds such as bupropion, mecamylamine, and 18-methoxycoronaridine block nicotinic acetylcholine receptors in the brain and have been proposed for treating nicotine addiction.
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 muscle-type nicotinic receptor is a type of nicotinic acetylcholine receptor consisting of the subunit combination (α1)2β1δε (adult receptor) or (α1)2β1δγ (fetal receptor). These receptors are found in neuromuscular junctions, where activation leads to an excitatory postsynaptic potential (EPSP), mainly by increased Na+ and K+ permeability.
Neuronal acetylcholine receptor subunit beta-4 is a protein that in humans is encoded by the CHRNB4 gene.
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].
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.
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.
Intrinsic activity (IA) and efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the potency of the drug and which is proportional to both efficacy and affinity. This use of the word "efficacy" was introduced by Stephenson (1956) to describe the way in which agonists vary in the response they produce, even when they occupy the same number of receptors. High efficacy agonists can produce the maximal response of the receptor system while occupying a relatively low proportion of the receptors in that system. There is a distinction between efficacy and intrinsic activity.
AR-R17779 is a drug that acts as a potent and selective full agonist for the α7 subtype of neural nicotinic acetylcholine receptors. It has nootropic effects in animal studies, but its effects do not substitute for those of nicotine. It has also been studied as a potential novel treatment for arthritis.
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.
A-366,833 is a drug developed by Abbott, which acts as an agonist at neural nicotinic acetylcholine receptors selective for the α4β2 subtype, and has been researched for use as an analgesic, although it has not passed clinical trials. Its structure has a nicotinonitrile (3-cyanopyridine) core bound through C5 to the N6 of (1R,5S)-3,6-diazabicyclo[3.2.0]heptane.
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.
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