Naltrindole is a highly potent, highly selective

delta opioid receptor Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D (NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also r ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

used in biomedical research. In May 2012 a paper was published in ''

Nature Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...

'' with the structure of naltrindole in complex with the mouse δ-opioid G-protein coupled receptor, solved by X-ray crystallography.

Drug design

Since

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

compounds are unable to cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

, researchers developed naltrindole to be a non-peptide antagonist analog of the

delta Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D (NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also re ...

-preferring endogenous opiate

enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...

. Enkephalin contains an

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

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 Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environmen ...

molecule to the C-ring of

naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...

morphinan Morphinan is the prototype chemical structure of a large chemical class of psychoactive drugs, consisting of opiate analgesics, cough suppressants, and dissociative hallucinogens, among others. Structure Morphinan has a phenanthrene core stru ...

base successfully produced a drug with the high receptor affinity of naltrexone, but which binds almost exclusively to the delta opioid receptor.

References

{{Opioid receptor modulators Delta-opioid receptor antagonists 4,5-Epoxymorphinans Indolomorphinans Phenols Tertiary alcohols Semisynthetic opioids