Naltrindole

Naltrindole

Systematic (IUPAC) name
17-Cyclopropylmethyl-6,7-dehydro-4,5-epoxy -3,14-dihydroxy-6,7,2',3'-indolomorphinan
Clinical data
Pregnancy cat.	?
Legal status	?
Routes	IV
Identifiers
CAS number	111555-53-4
ATC code	None
PubChem	CID 5497186
IUPHAR ligand	1641
ChemSpider	4593753 Y
ChEMBL	CHEMBL567175 Y
Chemical data
Formula	C26H26N2O3
Mol. mass	414.496 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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 Y Key:WIYUZYBFCWCCQJ-IFKAHUTRSA-N Y
Y(what is this?)  (verify)

Naltrindole is a highly potent, highly selective delta opioid receptor antagonist used in biomedical research.

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^[1]. 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^[2].

References

1. ^ 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
2. ^ 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