RESEARCH MONOGRAPH · KDC-MN-1353

Bradanicline

May 10, 2026 Kodiac biolabs Research Revised May 22, 2026 3 min read

Selective alpha-7 nicotinic acetylcholine receptor full agonist

A quinuclidine benzofuran-2-carboxamide developed at Targacept as a selective alpha-7 nicotinic full agonist with binding affinity of 1.4 nanomolar at the human alpha-7 receptor, advanced through Phase 2 development for schizophrenia cognitive impairment with a positive 12-week exploratory trial followed by a negative larger 24-week confirmatory trial, subsequently licensed to Anvylic Therapeutics for Tourette syndrome.

Abstract

Bradanicline (development codes TC-5619 and ATA-101) is a small-molecule highly selective full agonist of the alpha-7 subtype of the neuronal nicotinic acetylcholine receptor, originated at Targacept Pharmaceuticals from a quinuclidine benzofuran-2-carboxamide chemistry program in the mid-2000s. The compound binds the human alpha-7 receptor with a Ki of approximately 1.4 nanomolar, slightly higher affinity than encenicline (Ki approximately 4 nanomolar), and exhibits functional intrinsic activity of approximately 80 to 90 percent of the acetylcholine maximum response in heterologous expression systems, placing it in the high-efficacy stratum as a full agonist rather than the partial-agonist class that encenicline and tropisetron occupy. The compound was advanced through Phase 2 in 185 schizophrenia patients (Lieberman et al. 2013) at 5 milligrams once daily for 12 weeks with statistically significant improvement on the Groton Maze Learning Task and the Scale for Assessment of Negative Symptoms. A larger confirmatory Phase 2 trial (Walling et al. 2016) in 477 schizophrenia outpatients at 5 or 50 milligrams once daily for 24 weeks did not support a benefit. Targacept terminated the cognitive impairment program in 2013; the compound was subsequently licensed to Anvylic Therapeutics for Tourette syndrome. Notably, bradanicline did not produce the severe gastrointestinal toxicity that triggered the September 2015 FDA clinical hold on encenicline.

Mechanism of action

Selective full agonism at the orthosteric site of the alpha-7 nicotinic acetylcholine receptor. Ki 1.4 nanomolar at human alpha-7; functional intrinsic activity 80-90 percent of acetylcholine maximum (full agonist); selectivity over alpha-4-beta-2 and other neuronal nicotinic subtypes greater than 100-fold; brain penetration in rodent species supports central nervous system pharmacology at clinical doses.

Reported research dose ranges

Phase 2 schizophrenia: 5 mg per oral administration once daily for 12 weeks (Lieberman 2013) or 5 or 50 mg once daily for 24 weeks (Walling 2016). Phase 1 single ascending-dose to 100 mg in healthy volunteers. Research applications: in vitro 0.1-10 micromolar; rodent in vivo 0.3-10 mg/kg.

Selected references

  1. Hauser TA et al. TC-5619: an alpha-7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia. Biochem Pharmacol. 2009;78(7):803-812.
  2. Lieberman JA et al. A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology. 2013;38(6):968-975.
  3. Walling D et al. Phase 2 trial of an alpha-7 nicotinic receptor agonist (TC-5619) in negative and cognitive symptoms of schizophrenia. Schizophr Bull. 2016;42(2):335-343.
  4. Mazurov AA et al. Discovery of (2S,3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (TC-5619), a selective alpha-7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders. J Med Chem. 2012;55(22):9793-9809.
  5. Olincy A, Stevens KE. Failure of clinical trials in schizophrenia cognitive enhancement: lessons from encenicline. Schizophr Res. 2017;186:5-10.

Read the full monograph

The full reference document covers compound identification with chemistry and synthesis, discovery and developmental history, mechanism of action across molecular targets with quantitative receptor pharmacology, comprehensive pharmacokinetics, indication-by-indication clinical evidence base, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, adverse event signal, and a structured comparative assessment of five alpha-7 nicotinic acetylcholine receptor candidates judged against five competency standards. Embedded inline below; download for offline reading.

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