Tebanicline (ebanicline, ABT-594) is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

of the potent

poison dart frog Poison dart frog (also known as dart-poison frog, poison frog or formerly known as poison arrow frog) is the common name of a group of frogs in the family Dendrobatidae which are native to tropical Central and South America. These species are ...

-derived compound

epibatidine Epibatidine is a chlorinated alkaloid that is secreted by the Ecuadoran frog '' Epipedobates anthonyi'' and poison dart frogs from the ''Ameerega'' genus. It was discovered by John W. Daly in 1974, but its structure was not fully elucidated u ...

, which is about 200 times stronger than

morphine Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...

as an

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against

neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...

in both animal and human trials, but with far less toxicity than its parent compound. It acts as a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

at neuronal

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

s, binding to both the α3β4 and the

α4β2 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 pr ...

subtypes In programming language theory, subtyping (also called subtype polymorphism or inclusion polymorphism) is a form of type polymorphism. A ''subtype'' is a datatype that is related to another datatype (the ''supertype'') by some notion of substit ...

. Tebanicline progressed to Phase II clinical trials in humans, but was dropped from further development due to unacceptable incidence of

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

side effects. However, further research in this area is ongoing, and the development of nicotinic acetylcholine receptor agonists is ongoing. No agents from this class have successfully completed human clinical trials due to their unacceptable side effect profiles. CNS Rev:

References

{{Nicotinic acetylcholine receptor modulators Analgesics Pyridines Nicotinic agonists Stimulants Chloroarenes Phenol ethers Azetidines

See also

References