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 (mu, delta, and kappa), ADL-5859 appears to be selective and only activates the delta receptor.{{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}} with a Ki 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.
Multiple tests have shown its efficacy as an analgesic.{{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}} It also did not seem to be a convulsant, unlike some other delta agonist opioids.{{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}}