naltrindole
{{short description|Chemical compound}}
{{Drugbox
| verifiedrevid = 430795050
| IUPAC_name = 17-Cyclopropylmethyl-6,7-dehydro-4,5-epoxy -3,14-dihydroxy-6,7,2',3'-indolomorphinan
| image = naltrindole.png
| image_class = skin-invert-image
| tradename =
| routes_of_administration = IV
| metabolism =
| excretion =
| CAS_number = 111555-53-4
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = G167Z38QA4
| ATC_prefix = none
| PubChem = 5497186
| IUPHAR_ligand = 1641
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4593753
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 567175
| C=26 | H=26 | N=2 | O=3
| smiles = Oc4c3O[C@H]7c2c(c1ccccc1[nH]2)C[C@@]6(O)[C@H]5N(CC[C@@]67c3c(cc4)C5)CC8CC8
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C26H26N2O3/c29-19-8-7-15-11-20-26(30)12-17-16-3-1-2-4-18(16)27-22(17)24-25(26,21(15)23(19)31-24)9-10-28(20)13-14-5-6-14/h1-4,7-8,14,20,24,27,29-30H,5-6,9-13H2/t20-,24+,25+,26-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WIYUZYBFCWCCQJ-IFKAHUTRSA-N
}}
Naltrindole is a highly potent, highly selective delta opioid receptor antagonist used in biomedical research. In May 2012 a paper was published in Nature with the structure of naltrindole in complex with the mouse δ-opioid G-protein coupled receptor, solved by X-ray crystallography.{{cite journal | vauthors = Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK | title = Structure of the δ-opioid receptor bound to naltrindole | journal = Nature | volume = 485 | issue = 7398 | pages = 400–4 | date = May 2012 | pmid = 22596164 | pmc = 3523198 | doi = 10.1038/nature11111 | bibcode = 2012Natur.485..400G }}
Drug design
Since peptide compounds are unable to cross the blood–brain barrier, researchers developed naltrindole to be a non-peptide antagonist analog of the delta-preferring endogenous opiate enkephalin. Enkephalin contains an aromatic phenyl group on its Phe4 residue, which was hypothesized to be the "address" sequence responsible for the opiate's delta opioid receptor affinity.{{cite journal | vauthors = Lipkowski AW, Tam SW, Portoghese PS | title = Peptides as receptor selectivity modulators of opiate pharmacophores | journal = Journal of Medicinal Chemistry | volume = 29 | issue = 7 | pages = 1222–5 | date = July 1986 | pmid = 2879914 | doi = 10.1021/jm00157a018 }} Thus, attachment of a phenyl-containing indole molecule to the C-ring of naltrexone's morphinan base successfully produced a drug with the high receptor affinity of naltrexone, but which binds almost exclusively to the delta opioid receptor.{{cite journal | vauthors = Portoghese PS, Sultana M, Takemori AE | title = Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist | journal = European Journal of Pharmacology | volume = 146 | issue = 1 | pages = 185–6 | date = January 1988 | pmid = 2832195 | doi = 10.1016/0014-2999(88)90502-X }}
References
{{Reflist|2}}
{{Opioid receptor modulators}}
Category:Delta-opioid receptor antagonists