View source for ADL-5859

{{Short description|Selective delta opioid receptor agonist}}
{{Chembox
| Name           = ADL-5859
| ImageFile      = ADL-5859.svg
| IUPACName      = ''N'',''N''-Diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide
| Section1       = {{Chembox Identifiers
| CASNo          = 850305-06-5
| ChEMBL = 494480
| ChemSpiderID = 	9592841
| DrugBank = DB05050
| IUPHAR_ligand = 9004
| PubChem        = 11417954
| UNII = FA554TW3UP
| StdInChI=1S/C24H28N2O3/c1-3-26(4-2)23(28)18-10-8-17(9-11-18)19-16-24(12-14-25-15-13-24)29-21-7-5-6-20(27)22(19)21/h5-11,16,25,27H,3-4,12-15H2,1-2H3
| StdInChIKey = OPIKUXLJQFYMSC-UHFFFAOYSA-N
| SMILES = CCN(CC)C(=O)C1=CC=C(C=C1)C2=CC3(CCNCC3)OC4=CC=CC(=C42)O
}}
| Section2       = {{Chembox Properties
|C=24 |H=28 |N=2 |O=3
}}
|Section8={{Chembox Related
| OtherCompounds = [[ADL-5747]]
}}
}}
'''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 ==
Like all opioid drugs, ADL-5859 activates opioid receptors, but where as traditional opioids (such as [[oxycodone]]) activate the three main receptors ([[Μ-opioid receptor|mu]], [[Δ-opioid receptor|delta]], and [[Κ-opioid receptor|kappa]]), ADL-5859 appears to be selective and only activates the delta receptor.<ref name=":0">{{Cite journal |last1=Spahn |first1=Viola |last2=Stein |first2=Christoph |date=February 2017 |title=Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development |url=https://pubmed.ncbi.nlm.nih.gov/28001096/ |journal=Expert Opinion on Investigational Drugs |volume=26 |issue=2 |pages=155–160 |doi=10.1080/13543784.2017.1275562 |issn=1744-7658 |pmid=28001096}}</ref> with a K<sub>i</sub> of 20 nM
== Therapeutic potential ==
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, and euphoria.
ADL-5859 was also found to be orally active, which makes it easier to administer.<ref>{{Cite journal |last1=Le Bourdonnec |first1=Bertrand |last2=Windh |first2=Rolf T. |last3=Ajello |first3=Christopher W. |last4=Leister |first4=Lara K. |last5=Gu |first5=Minghua |last6=Chu |first6=Guo-Hua |last7=Tuthill |first7=Paul A. |last8=Barker |first8=William M. |last9=Koblish |first9=Michael |last10=Wiant |first10=Daniel D. |last11=Graczyk |first11=Thomas M. |last12=Belanger |first12=Serge |last13=Cassel |first13=Joel A. |last14=Feschenko |first14=Marina S. |last15=Brogdon |first15=Bernice L. |date=2008-10-09 |title=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) |url=https://pubmed.ncbi.nlm.nih.gov/18788723/ |journal=Journal of Medicinal Chemistry |volume=51 |issue=19 |pages=5893–5896 |doi=10.1021/jm8008986 |issn=1520-4804 |pmid=18788723}}</ref>
Multiple tests have shown its efficacy as an analgesic.<ref>{{Cite journal |last1=Nozaki |first1=Chihiro |last2=Le Bourdonnec |first2=Bertrand |last3=Reiss |first3=David |last4=Windh |first4=Rolf T. |last5=Little |first5=Patrick J. |last6=Dolle |first6=Roland E. |last7=Kieffer |first7=Brigitte L. |last8=Gavériaux-Ruff |first8=Claire |date=September 2012 |title=δ-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=342 |issue=3 |pages=799–807 |doi=10.1124/jpet.111.188987 |issn=1521-0103 |pmc=3422521 |pmid=22700431}}</ref><ref name=":0" /> It also did not seem to be a convulsant, unlike some other delta agonist opioids.<ref>{{Cite journal |last1=Chung |first1=Paul Chu Sin |last2=Boehrer |first2=Annie |last3=Stephan |first3=Aline |last4=Matifas |first4=Audrey |last5=Scherrer |first5=Grégory |last6=Darcq |first6=Emmanuel |last7=Befort |first7=Katia |last8=Kieffer |first8=Brigitte L. |date=2015-02-01 |title=Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures |journal=Behavioural Brain Research |volume=278 |pages=429–434 |doi=10.1016/j.bbr.2014.10.029 |issn=1872-7549 |pmc=4382405 |pmid=25447299}}</ref>
== References ==
{{Reflist}}
{{Opioid receptor modulators}}
[[Category:Synthetic opioids]]
[[Category:Delta-opioid receptor agonists]]
[[Category:Analgesics]]
[[Category:Chromanes]]
[[Category:Piperidines]]
[[Category:Spiro compounds]]
[[Category:Benzamides]]
[[Category:Diethylamino compounds]]