Naltrindole

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Naltrindole
Naltrindole.png
Systematic (IUPAC) name
17-Cyclopropylmethyl-6,7-dehydro-4,5-epoxy -3,14-dihydroxy-6,7,2',3'-indolomorphinan
Clinical data
IV
Identifiers
111555-53-4
None
PubChem CID 5497186
IUPHAR ligand 1641
ChemSpider 4593753 YesY
ChEMBL CHEMBL567175 YesY
Chemical data
Formula C26H26N2O3
414.496 g/mol
 YesY (what is this?)  (verify)

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.[1]

Drug design[edit]

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.[2] 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.[3]

References[edit]

  1. ^ Granier, S.; Manglik, A.; Kruse, A. C.; Kobilka, T. S.; Thian, F. S.; Weis, W. I.; Kobilka, B. K. (2012). "Structure of the δ-opioid receptor bound to naltrindole". Nature 485 (7398): 400–404. doi:10.1038/nature11111. PMC 3523198. PMID 22596164. 
  2. ^ Lipkowski, AW; Tam, SW; Portoghese, PS (Jul 1986). "Peptides as receptor selectivity modulators of opiate pharmacophores". Journal of Medicinal Chemistry 29 (7): 1222–5. doi:10.1021/jm00157a018. PMID 2879914. 
  3. ^ Portoghese, PS; Sultana, M; Takemori, AE (Jan 1988). "Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist". European Journal of Pharmacology 146 (1): 185–6. doi:10.1016/0014-2999(88)90502-X. PMID 2832195.