What does DOR stand for?

DOR stands for Delta-Opioid Receptor. The receptor is also referred to as OP1 in older pharmacological literature and DOP in some IUPHAR documents. The encoding gene is OPRD1.

What gene encodes the delta-opioid receptor?

The OPRD1 gene, located on chromosome 1 (1p35.3) in humans.

What is the difference between DOR and MOR?

Both are G-protein-coupled opioid receptors with a conserved signaling architecture. They differ in distribution, endogenous ligand preference, and pharmacology. MOR is the principal target of classical opioid analgesics; DOR is the principal target of the enkephalin peptides and has a distinct functional role.

Are kratom alkaloids active at DOR?

In published in vitro work, mitragynine and 7-hydroxymitragynine show antagonist or weak partial activity at DOR - distinct from classical DOR full agonists such as DPDPE. Mitragynine pseudoindoxyl was specifically characterized as a DOR antagonist in Varadi 2016.

Why does DOR antagonism matter for opioid pharmacology research?

Some preclinical research has hypothesized that combining MOR partial agonism with DOR antagonism may produce a different effect profile than balanced multi-receptor opioid activation. This hypothesis is part of why the kratom alkaloid receptor profile attracted research attention. Clinical implications of these in vitro findings have not been established.

What are the endogenous ligands at DOR?

The enkephalin peptides - Met-enkephalin and Leu-enkephalin - are the principal endogenous ligands at the delta-opioid receptor.

Receptor Pharmacology

Delta-Opioid Receptor (DOR)

At-a-glance comparison

Spec	Value
Receptor name	Delta-opioid receptor (DOR; also OP1, DOP)
Encoding gene	OPRD1 (chromosome 1p35.3 in humans)
Receptor superfamily	G-protein-coupled receptor (GPCR), Class A (rhodopsin-like)
Primary signaling	Inhibitory G-protein (Gαi/o); β-arrestin recruitment as alternative pathway
Endogenous ligands	Enkephalins (Met-enkephalin, Leu-enkephalin)
Reference exogenous agonists	DPDPE, SNC-80 (selective DOR agonists used in research)
Reference antagonists	Naltrindole, ICI-174,864
Kratom alkaloid activity (in vitro)	Mitragynine and 7-OH: typically reported as antagonist or weak partial activity; mitragynine pseudoindoxyl: characterized as DOR antagonist in Varadi 2016

What is the delta-opioid receptor?

The delta-opioid receptor is a cell-surface G-protein-coupled receptor encoded by the gene OPRD1. It is one of the four classical opioid receptor subtypes and shares a conserved signaling architecture with the mu-opioid receptor (MOR), kappa-opioid receptor (KOR), and nociceptin receptor (NOP). DOR is widely distributed in the central and peripheral nervous systems and is the principal target of the endogenous enkephalin peptides - Met-enkephalin and Leu-enkephalin.

DOR is an active subject of receptor-biology research in the academic literature. Selective DOR agonists such as DPDPE and SNC-80 have been used as research tools to characterize the receptor; selective DOR antagonists such as naltrindole are used to dissect the contribution of DOR to compound effects in research models.

Kratom alkaloids at the delta-opioid receptor

In published in vitro work, the kratom alkaloids mitragynine and 7-hydroxymitragynine generally show antagonist or weak partial activity at the delta-opioid receptor - a distinct profile from classical full agonists such as DPDPE or SNC-80. Mitragynine pseudoindoxyl, in the influential Varadi and colleagues (2016) characterization, was specifically described as a delta-opioid receptor antagonist combined with mu-opioid receptor partial agonism - a receptor profile that is part of why this rearrangement product attracted research attention.

The DOR profile of kratom alkaloids is one component of a broader receptor profile that includes activity at MOR, KOR, alpha-2 adrenergic receptors, and several serotonin receptor subtypes in published assays. These pharmacology findings come from cell-based and biochemical assays in academic and industry laboratories. They describe receptor-level interactions in research models only and should not be interpreted as evidence of safety, efficacy, or any clinical or therapeutic effect in humans.

How DOR signals

When activated, DOR couples to inhibitory heterotrimeric G-proteins (Gαi/o), reducing adenylate cyclase activity and modulating ion channels in a manner mechanistically similar to the other opioid receptors. After activation, DOR also recruits β-arrestin, mediating receptor desensitization and an alternative signaling cascade. The relative balance of G-protein and β-arrestin signaling at DOR is, as at MOR, the foundation of biased agonism - and is itself an active research area in the broader opioid pharmacology field.

Common questions about delta-opioid receptor (dor)

What does DOR stand for?: DOR stands for Delta-Opioid Receptor. The receptor is also referred to as OP1 in older pharmacological literature and DOP in some IUPHAR documents. The encoding gene is OPRD1.
What gene encodes the delta-opioid receptor?: The OPRD1 gene, located on chromosome 1 (1p35.3) in humans.
What is the difference between DOR and MOR?: Both are G-protein-coupled opioid receptors with a conserved signaling architecture. They differ in distribution, endogenous ligand preference, and pharmacology. MOR is the principal target of classical opioid analgesics; DOR is the principal target of the enkephalin peptides and has a distinct functional role.
Are kratom alkaloids active at DOR?: In published in vitro work, mitragynine and 7-hydroxymitragynine show antagonist or weak partial activity at DOR - distinct from classical DOR full agonists such as DPDPE. Mitragynine pseudoindoxyl was specifically characterized as a DOR antagonist in Varadi 2016.
Why does DOR antagonism matter for opioid pharmacology research?: Some preclinical research has hypothesized that combining MOR partial agonism with DOR antagonism may produce a different effect profile than balanced multi-receptor opioid activation. This hypothesis is part of why the kratom alkaloid receptor profile attracted research attention. Clinical implications of these in vitro findings have not been established.
What are the endogenous ligands at DOR?: The enkephalin peptides - Met-enkephalin and Leu-enkephalin - are the principal endogenous ligands at the delta-opioid receptor.

References

Varadi A, Marrone GF, Palmer TC, et al. (2016). Mitragynine/Corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism. J Med Chem. PMID 27513560.
Pradhan AA, Befort K, Nozaki C, et al. (2011). The delta opioid receptor: an evolving target for the treatment of brain disorders. Trends in Pharmacological Sciences.
Manglik A, et al. (2016). Structure-based discovery of opioid analgesics with reduced side effects. Nature.
International Union of Basic and Clinical Pharmacology. Delta-opioid receptor entry. https://www.guidetopharmacology.org

Important safety information:

Products containing 7-hydroxymitragynine (7-OH) are sold for adult use only (21+). These statements have not been evaluated by the U.S. Food and Drug Administration. Products are not intended to diagnose, treat, cure, or prevent any disease. The FDA has raised safety concerns regarding concentrated 7-OH products; consult a qualified healthcare professional before use. Do not operate vehicles or machinery after use. Keep out of reach of children and pets. Laws vary by state, buyers are responsible for knowing applicable law.