Aticaprant
Clinical data | |
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Other names | JNJ-67953964; CERC-501; LY-2456302 |
Routes of administration | By mouth[1] |
Pharmacokinetic data | |
Bioavailability | 25%[1] |
Elimination half-life | 30–40 hours[1] |
Identifiers | |
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JSmol) | |
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Aticaprant, also known by its developmental codes JNJ-67953964, CERC-501, and LY-2456302, is a
Aticaprant was originally developed by Eli Lilly, was under development by Cerecor for a time, and is now under development by Janssen Pharmaceuticals.[2] As of July 2022, it is in phase 3 clinical trials for major depressive disorder.[2] Like other kappa opioid antagonists currently under clinical investigation for the treatment of major depression, its efficacy may be compromised by the countervailing activation of pro-inflammatory cytokines in microglia within the CNS.[7]
Aticaprant was also under development for the treatment of
Pharmacology
Pharmacodynamics
Aticaprant is a
Positron emission tomography imaging revealed that brain KORs were almost completely saturated by the drug 2.5 hours following a single dose of 10 mg, which supported the 4 mg to 25 mg dosages that aticaprant is being explored at in clinical trials.[13][14] Occupancy was 35% for a 0.5 mg dose and 94% for a 10 mg dose.[15][14] At 24 hours post-dose, receptor occupancy was 19% for 0.5 mg and 82% for 25 mg.[15][14] No serious side effects were observed, and all side effects seen were mild to moderate and were not thought to be due to aticaprant.[14]
Pharmacokinetics
The
History
Aticaprant was originally developed by Eli Lilly under the code name LY-2456302.[2] It first appeared in the scientific literature in 2010 or 2011.[16][17] The compound was first patented in 2009.[18]
In February 2015, Cerecor Inc. announced that they had acquired the rights from Eli Lilly to develop and commercialize LY-2456302 (under the new developmental code CERC-501).[19]
As of 2016, aticaprant has reached
In August 2017, it was announced that Cerecor had sold its rights to aticaprant to Janssen Pharmaceuticals.[22][21] Janssen was also experimenting with esketamine for the treatment of depression as of 2017.[21]
Research
In addition to
See also
- κ-Opioid receptor § Antagonists
- List of investigational antidepressants
References
- ^ PMID 27213169.
- ^ a b c d e f g h "CERC 501". Adis Insight. 30 January 2018.
- ^ S2CID 231908782.
- ^ S2CID 226305229.
- S2CID 256839849.
- S2CID 45232796.
- PMID 34826432.
- S2CID 3230414.
- S2CID 14814449.
- ^ PMID 25637376.
- PMID 29422497.
- ^ PMID 24690494.
- ^ a b "Publication Reports Human Brain Penetration and Target Engagement of Cerecor's Oral Kappa Opioid Receptor Antagonist, CERC-501". BusinessWire. 11 December 2015.
- ^ PMID 26628406.
- ^ S2CID 236947969.
- PMID 23353688.
- PMID 21958337.
- ^ "WO2009094260A1 - Kappa selective opioid receptor antagonist". Google Patents. 13 January 2009. Retrieved 29 August 2022.
- ^ "Cerecor Bolsters Clinical Pipeline with Acquisition of Phase 2-ready Kappa Opioid Receptor Antagonist from Eli Lilly and Company". cerecor.com. February 20, 2015. Archived from the original on 2015-02-23. Retrieved March 18, 2015.
- ISBN 978-1-84973-365-6.
- ^ a b c Bushey R (August 2017). "J&J Adds New Depression Drug to Portfolio". Drug Discovery and Development Magazine.
- ^ "Cerecor Announces Divestiture of CERC-501 to Janssen Pharmaceuticals, Inc". Marketwired. August 2017. Archived from the original on 2017-09-01. Retrieved 2017-09-01.
Further reading
- Carlezon WA, Krystal AD (October 2016). "Kappa-Opioid Antagonists for Psychiatric Disorders: From Bench to Clinical Trials". Depression and Anxiety. 33 (10): 895–906. PMID 27699938.
- Li W, Sun H, Chen H, Yang X, Xiao L, Liu R, et al. (2016). "Major Depressive Disorder and Kappa Opioid Receptor Antagonists". Translational Perioperative and Pain Medicine. 1 (2): 4–16. PMID 27213169.
- Dhir A (January 2017). "Investigational drugs for treating major depressive disorder". Expert Opinion on Investigational Drugs. 26 (1): 9–24. S2CID 45232796.
- Reed B, Butelman ER, Kreek MJ (2017). "Endogenous opioid system in addiction and addiction-related behaviors". Current Opinion in Behavioral Sciences. 13: 196–202. S2CID 53149180.
- Rakesh G, Pae CU, Masand PS (August 2017). "Beyond serotonin: newer antidepressants in the future". Expert Review of Neurotherapeutics. 17 (8): 777–790. S2CID 205823807.
- Helal MA, Habib ES, Chittiboyina AG (December 2017). "Selective kappa opioid antagonists for treatment of addiction, are we there yet?". European Journal of Medicinal Chemistry. 141: 632–647. PMID 29107424.
- McHugh KL, Kelly JP (2018). "Modulation of the central opioid system as an antidepressant target in rodent models". The Opioid System as the Interface between the Brain's Cognitive and Motivational Systems. Progress in Brain Research. Vol. 239. pp. 49–87. PMID 30314569.
- Bailey SJ, Husbands SM (June 2018). "Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?". Neuronal Signaling. 2 (2): NS20170145. PMID 32714584.
- Chavkin C (August 2018). "Kappa-opioid antagonists as stress resilience medications for the treatment of alcohol use disorders". Neuropsychopharmacology. 43 (9): 1803–1804. PMID 29752444.
- Krystal AD, Pizzagalli DA, Mathew SJ, Sanacora G, Keefe R, Song A, et al. (December 2018). "The first implementation of the NIMH FAST-FAIL approach to psychiatric drug development". Nature Reviews. Drug Discovery. 18 (1): 82–84. PMID 30591715.
- Lazar MA, McIntyre RS (2019). "Novel Therapeutic Targets for Major Depressive Disorder". Neurobiology of Depression. pp. 383–400. S2CID 86782597.
- Browne CA, Lucki I (September 2019). "Targeting opioid dysregulation in depression for the development of novel therapeutics". Pharmacology & Therapeutics. 201: 51–76. PMID 31051197.
- Banks ML (2020). "The Rise and Fall of Kappa-Opioid Receptors in Drug Abuse Research". In Nader MA, Hurd YL (eds.). Substance Use Disorders. Handbook of Experimental Pharmacology. Vol. 258. pp. 147–165. PMID 31463605.
- Browne CA, Jacobson ML, Lucki I (2020). "Novel Targets to Treat Depression: Opioid-Based Therapeutics". Harvard Review of Psychiatry. 28 (1): 40–59. S2CID 210120636.
- Jacobson ML, Browne CA, Lucki I (January 2020). "Kappa Opioid Receptor Antagonists as Potential Therapeutics for Stress-Related Disorders". Annual Review of Pharmacology and Toxicology. 60: 615–636. S2CID 210121357.
- Mercadante S, Romualdi P (2020). "The Therapeutic Potential of Novel Kappa Opioid Receptor-based Treatments". Current Medicinal Chemistry. 27 (12): 2012–2020. S2CID 58558833.