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
Legal status ?
Routes IV
Identifiers
CAS number 111555-53-4
ATC code None
PubChem CID 5497186
IUPHAR ligand 1641
ChemSpider 4593753 YesY
ChEMBL CHEMBL567175 YesY
Chemical data
Formula C26H26N2O3 
Mol. mass 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. ^ S. Granier, A. Manglik, A. C. Kruse, T. S. Kobilka, F. S. Thian, W. I. Weis & B. K. Kobilka. "Structure of the δ-opioid receptor bound to naltrindole." nature. Nature 485, 400–404 (17 May 2012). doi:10.1038/nature11111 PMID 22596164
  2. ^ Lipkowski AW, Tam SW, Portoghese PS. "Peptides as receptor selectivity modulators of opiate pharmacophores." Journal of Medicinal Chemistry. 1986 Jul;29(7):1222-5. PMID 2879914
  3. ^ Portoghese PS, Sultana M, Takemori AE. "Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist." European Journal of Pharmacology. 1988 Jan 27;146(1):185-6. doi:10.1016/0014-2999(88)90502-X PMID 2832195