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. 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. == References ==