ADL-5859
-4-yl)-.png)
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| Names | |
|---|---|
| IUPAC name
N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide
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| Identifiers | |
PubChem CID
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| Properties | |
| C24H28N2O3 | |
| Molar mass | 392.499 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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ADL-5859, also known as Compound 20 is an opioid drug that is selective for the Δ-opioid receptor, it is being investigated as an alternative to traditional opioids in pain management.
Mechanism of action
[edit]Like all opioid drugs, ADL-5859 activates opioid receptors, but where as traditional opioids (such as oxycodone) activate the three main receptors (mu, delta and kappa), ADL-5859 appears to be selective and only activates the delta receptor.[1] with a Ki of 20nM[2]
Therapeutic potential
[edit]Like other opioids, it has potential in pain management, however, by being selective for the delta receptor, multiple undesirable side effects of traditional opioids are not present, such as respiratory depression, sedation, euphoria.
ADL-5859 was also found to be orally active, which makes it easier to administer.[3]
Multiple tests have shown its efficacy as an analgesic[4][1]. It also did not seem to be a convulsant, unlike some other delta agonist opioids.[5]
References
[edit]- ^ a b Spahn, Viola; Stein, Christoph (February 2017). "Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development". Expert Opinion on Investigational Drugs. 26 (2): 155–160. doi:10.1080/13543784.2017.1275562. ISSN 1744-7658. PMID 28001096.
- ^ "ADL-5859 hydrochloride | Opioid Receptor Agonist | MedChemExpress".
- ^ Le Bourdonnec, Bertrand; Windh, Rolf T.; Ajello, Christopher W.; Leister, Lara K.; Gu, Minghua; Chu, Guo-Hua; Tuthill, Paul A.; Barker, William M.; Koblish, Michael; Wiant, Daniel D.; Graczyk, Thomas M.; Belanger, Serge; Cassel, Joel A.; Feschenko, Marina S.; Brogdon, Bernice L. (2008-10-09). "Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859)". Journal of Medicinal Chemistry. 51 (19): 5893–5896. doi:10.1021/jm8008986. ISSN 1520-4804. PMID 18788723.
- ^ Nozaki, Chihiro; Le Bourdonnec, Bertrand; Reiss, David; Windh, Rolf T.; Little, Patrick J.; Dolle, Roland E.; Kieffer, Brigitte L.; Gavériaux-Ruff, Claire (September 2012). "δ-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization". The Journal of Pharmacology and Experimental Therapeutics. 342 (3): 799–807. doi:10.1124/jpet.111.188987. ISSN 1521-0103. PMC 3422521. PMID 22700431.
- ^ Chung, Paul Chu Sin; Boehrer, Annie; Stephan, Aline; Matifas, Audrey; Scherrer, Grégory; Darcq, Emmanuel; Befort, Katia; Kieffer, Brigitte L. (2015-02-01). "Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures". Behavioural Brain Research. 278: 429–434. doi:10.1016/j.bbr.2014.10.029. ISSN 1872-7549. PMC 4382405. PMID 25447299.