ABT-925, also known as A-437203 or as LU-201640, is a selective dopamine D3 receptor antagonist which was under development for the treatment of schizophrenia but was never marketed.[1][3][2] It is taken orally.[1][2]
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| Other names | ABT925; A-437203; A437203; BSF-201640; BSF201640; DTA-201; DTA201; LU-201640; LU201640 |
| Routes of administration | Oral[1][2] |
| Drug class | Dopamine D3 receptor antagonist |
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| Formula | C20H27F3N6OS |
| Molar mass | 456.53 g·mol−1 |
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The drug shows affinity for the dopamine D3 receptor and to a much lesser extent for the dopamine D2 receptor, with Ki values of 0.97–3.2 nM and 75 nM, respectively, and with 45- to 120-fold selectivity for the dopamine D3 receptor over the dopamine D2 receptor.[4][5][2] It showed little activity in classical tests of antipsychotic-like activity in rodents, for instance inhibition of methamphetamine-induced hyperlocomotion and inhibition of apomorphine-induced climbing behavior.[5][6] The drug does not produce catalepsy and does not affect prolactin levels in rodents.[5][6] The occupancy of the dopamine D3 receptor by ABT-925 has been studied in humans.[4][7][8]
ABT-925 was first described in the scientific literature by 1997.[5][9][6] At the time, it was the most potent and selective dopamine D3 receptor antagonist yet known.[5] In addition, the drug has been said to have been the first selective dopamine D3 receptor antagonist.[4] It was under development by Abbott Laboratories.[1][3] The drug reached phase 2 clinical trials prior to the discontinuation of its development.[1][3] ABT-925 is known to have been in active phase 2 trials between 2001 and 2007.[1] It failed to show antipsychotic effectiveness in acute schizophrenia in a phase 2 trial published in 2011.[10][4][2]
See also
editReferences
edit- 1 2 3 4 5 6 "ABT 925". AdisInsight. 24 January 2013. Retrieved 7 June 2026.
- 1 2 3 4 5 Redden L, Rendenbach-Mueller B, Abi-Saab WM, Katz DA, Goenjian A, Robieson WZ, et al. (April 2011). "A double-blind, randomized, placebo-controlled study of the dopamine D₃ receptor antagonist ABT-925 in patients with acute schizophrenia". Journal of Clinical Psychopharmacology. 31 (2): 221–225. doi:10.1097/JCP.0b013e31820e4818. PMID 21346607.
- 1 2 3 "Delving into the Latest Updates on A-437203 with Synapse". Synapse. 30 May 2026. Retrieved 7 June 2026.
- 1 2 3 4 Gross G, Wicke K, Drescher KU (February 2013). "Dopamine D₃ receptor antagonism--still a therapeutic option for the treatment of schizophrenia". Naunyn-Schmiedeberg's Archives of Pharmacology. 386 (2): 155–166. doi:10.1007/s00210-012-0806-3. PMID 23128852.
- 1 2 3 4 5 Gross G, Bialojan S, Drescher K, Freeman AS, Garcia-Ladona FJ, Höger T, et al. (1997). "S. 21.02 Evaluation of D3 receptor antagonists". European Neuropsychopharmacology. 7: S120. doi:10.1016/S0924-977X(97)88428-3.
- 1 2 3 Drescher KU, Garcia-Ladona FJ, Teschendorf HJ, Traut M, Unger L, Wicke KM, et al. (November 2002). In vivo effects of the selective dopamine D3 receptor antagonist A-437203. Abstr.-Soc. Neurosci. Vol. 28.
- ↑ Graff-Guerrero A, Redden L, Abi-Saab W, Katz DA, Houle S, Barsoum P, et al. (April 2010). "Blockade of [11C](+)-PHNO binding in human subjects by the dopamine D3 receptor antagonist ABT-925". The International Journal of Neuropsychopharmacology. 13 (3): 273–287. doi:10.1017/S1461145709990642. PMID 19751545.
- ↑ Day M, Bain E, Marek G, Saltarelli M, Fox GB (April 2010). "D3 receptor target engagement in humans with ABT-925 using [11C](+)-PHNO PET". The International Journal of Neuropsychopharmacology. 13 (3): 291–292. doi:10.1017/S1461145710000180. PMID 20196920.
- ↑ Unger L, Garcia-Ladona F, Wernet W, Sokoloff P, Wicke KM, Gross G (2002). In vitro characterization of the selective dopamine D3 receptor antagonist A-437203. Abstr.-Soc. Neurosci. Vol. 28.
- ↑ Pich EM, Collo G (September 2015). "Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs". European Neuropsychopharmacology. 25 (9): 1437–1447. doi:10.1016/j.euroneuro.2015.07.012. PMID 26298833.