# Oxytocin receptor

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Genes on human chromosome 3

OXTR Identifiers Aliases OXTR, OT-R, oxytocin receptor External IDs OMIM: 167055; MGI: 109147; HomoloGene: 20255; GeneCards: OXTR; OMA:OXTR - orthologs Gene location (Mouse) Chr. Chromosome 6 (mouse)[1] Band 6|6 E3 Start 112,450,644 bp[1] End 112,466,904 bp[1] RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in mammary gland lumbar subsegment of spinal cord cervix white adipose tissue islet of Langerhans ciliary body pineal gland mesenteric lymph nodes dentate gyrus of hippocampal formation granule cell adrenal gland BioGPS More reference expression data Gene ontology Molecular function G protein-coupled receptor activity peptide binding signal transducer activity peptide hormone binding vasopressin receptor activity oxytocin receptor activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane intracellular anatomical structure microvillus apical plasma membrane Biological process response to cocaine positive regulation of synapse assembly positive regulation of norepinephrine secretion response to cytokine maternal process involved in parturition response to estradiol muscle contraction response to anoxia response to organic cyclic compound eating behavior ejaculation estrous cycle positive regulation of cytosolic calcium ion concentration response to progesterone response to amphetamine ERK1 and ERK2 cascade regulation of systemic arterial blood pressure by vasopressin response to steroid hormone response to peptide hormone negative regulation of gastric acid secretion memory positive regulation of synaptic transmission, GABAergic response to peptide development of the heart cell surface receptor signaling pathway telencephalon development sleep cellular response to hormone stimulus positive regulation of blood pressure positive regulation of synaptic transmission, glutamatergic Maternal behavior positive regulation of vasoconstriction social behavior positive regulation of penile erection lactation digestive tract development regulation of digestive system process signal transduction positive regulation of uterine smooth muscle contraction suckling behavior female pregnancy G protein-coupled receptor signaling pathway positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 5021 18430 Ensembl ENSG00000180914 ENSMUSG00000049112 UniProt P30559 P97926 RefSeq (mRNA) NM_000916 NM_001081147 RefSeq (protein) NP_000907 NP_001341582 NP_001341583 NP_001341584 NP_001341585 NP_001074616 Location (UCSC) n/a Chr 6: 112.45 – 112.47 Mb PubMed search [2] [3] Wikidata View/Edit Human View/Edit Mouse

The **oxytocin receptor**, also known as **OXTR**, is a [protein](/source/Protein) which functions as [receptor](/source/Receptor_(biochemistry)) for the [hormone](/source/Hormone) and [neurotransmitter](/source/Neurotransmitter) [oxytocin](/source/Oxytocin).[4][5] In humans, the oxytocin receptor is encoded by the *OXTR* [gene](/source/Gene)[6][7] which has been localized to human [chromosome 3p25](/source/Chromosome_3).[8]

Evolutionary tree of the oxytocin, [vasotocin](/source/Vasotocin), [mesotocin](https://en.wikipedia.org/w/index.php?title=Mesotocin&action=edit&redlink=1) and [isotocin](https://en.wikipedia.org/w/index.php?title=Isotocin&action=edit&redlink=1) receptors and their ligands. From Koechbach et al.[9]

## Function and location

The OXTR protein belongs to the [G-protein coupled receptor](/source/G_protein-coupled_receptor) family, specifically [Gq](/source/Gq_alpha_subunit),[4] and acts as a receptor for oxytocin. Its activity is mediated by [G proteins](/source/G_protein) that activate several different [second messenger](/source/Second_messenger) systems.[10][11]

Oxytocin receptors are expressed by the [myoepithelial cells](/source/Myoepithelial_cell) of the [mammary gland](/source/Mammary_gland), and in both the [myometrium](/source/Myometrium) and [endometrium](/source/Endometrium) of the [uterus](/source/Uterus) at the end of [pregnancy](/source/Pregnancy). The oxytocin-oxytocin receptor system plays an important role as an inducer of uterine contractions during [parturition](/source/Parturition) and of milk ejection.

OXTR is also associated with the central nervous system. The gene is believed to play a major role in social, cognitive, and emotional behavior.[12] A decrease in OXTR expression by methylation of the *OXTR* gene is associated with [callous and unemotional traits](/source/Callous_and_unemotional_traits) in adolescence, rigid thinking in [anorexia nervosa](/source/Anorexia_nervosa), problems with facial and emotional recognition, and difficulties in the [affect regulation](https://en.wikipedia.org/w/index.php?title=Regulation_of_affect&action=edit&redlink=1). A reduction in this gene is believed to lead to prenatal stress, postnatal depression, and social anxiety.[12] Further research must be gathered before concluding these findings, however strong evidence is pointing in this direction. Studies on *OXTR* methylation—which downregulates oxytocin mechanisms—suggest this process is associated with increased gray matter density in the amygdala, implicating *OXTR* regulation in stress and parasympathetic regulation.[13]

In some mammals, oxytocin receptors are also found in the [kidney](/source/Kidney) and [heart](/source/Heart).

### Mesolimbic dopamine pathways

The oxytocinergic circuit projecting from the [paraventricular hypothalamic nucleus](/source/Paraventricular_hypothalamic_nucleus) (PVN) innervates the [ventral tegmental area](/source/Ventral_tegmental_area) (VTA) dopaminergic neurons that project to the [nucleus accumbens](/source/Nucleus_accumbens), i.e., the [mesolimbic pathway](/source/Mesolimbic_pathway).[14] Activation of the PVN→VTA projection by oxytocin affects sexual, social, and addictive behavior via this link to the mesolimbic pathway;[14] specifically, oxytocin exerts a prosexual and prosocial effect in this region.[14]

## Polymorphism

The receptors for oxytocin (OXTR) have genetic differences with varied effects on individual behavior. The [polymorphism](/source/Polymorphism_(biology)) (rs53576) occurs on the third [intron](/source/Intron) of OXTR in three types: GG, AG, AA. The GG allele is connected with oxytocin levels in people [*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]. A-allele carrier individuals are associated with more sensitivity to stress, fewer social skills, and more mental health issues than the GG-carriers.[15][*[qualify evidence](https://en.wikipedia.org/wiki/Wikipedia:Qualify_evidence)*]

In a study looking at [empathy](/source/Empathy) and [stress](/source/Stress_(biology)), individuals with the allele GG scored higher than A-carrier individuals in a "Reading the Mind in the Eyes" test. GG carriers, with their naturally higher levels of oxytocin, were better able to distinguish between emotions.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*] A-allele carriers responded with more stress to stressful situations than GG-allele carriers.[16][*[further explanation needed](https://en.wikipedia.org/wiki/Wikipedia:Please_clarify)*] A-allele carriers had lower scores on psychological resources, like optimism, mastery, and self-esteem, than GG individuals when measured with factor analysis for depressive symptomology and psychological resources, along with the [Beck Depression Inventory](/source/Beck_Depression_Inventory). A-allele carriers had higher depressive symptomology and lower psychological resources than GG individuals.[15][*[qualify evidence](https://en.wikipedia.org/wiki/Wikipedia:Qualify_evidence)*] A-allele individuals scored lower in human sociality than GG people on a [Tridimensional Personality Questionnaire](/source/Tridimensional_Personality_Questionnaire). AA individuals had the lowest amygdala activation while processing emotionally salient information and those with GG had the highest activity when tested using BOLD during an [fMRI](/source/FMRI).[17] On the other hand, variations at the CD38 rs3796863 and OXTR rs53576 loci were not associated with psychosocial characteristics of adolescents assessed with the [Strengths and Difficulties Questionnaire (SDQ)](/source/Strengths_and_Difficulties_Questionnaire_(SDQ)); in studies with a similar design, authors recommend replication with larger samples and greater power to detect small effects, especially in age–sex subgroups of adolescents.[18]

The frequency of the A allele varies among ethnic groups, being significantly more common among East Asians than Europeans.[19][*[quantify](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers)*][*[additional citation(s) needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

Some evidence suggests an association between OXTR gene polymorphism, [IQ](/source/IQ), and [autism spectrum disorder](/source/Autism_spectrum_disorder) (ASD).[20] Studies have done research focusing on variants in the third intron of the gene, a region that is strongly correlated with personality traits and ASD. OXTR knockout mice have shown abnormal behaviors such as social impairments and aggressiveness. These abnormalities can be reduced with oxytocin or oxytocin agonist administration. Overall, the study suggests that rare variants are considerably more abundant in individuals with ASD compared to that of a normal individual, however further research with larger sample sizes must be completed before concluding any information.[21]

## Ligands

Several selective [ligands](/source/Ligand) for the oxytocin receptor have recently been developed, but close similarity between the oxytocin and related [vasopressin](/source/Vasopressin) receptors make it difficult to achieve high selectivity with peptide derivatives.[22][23] However the search for a druggable, non-peptide template has led to several potent, highly selective, orally bioavailable oxytocin antagonists.[24] [Oxytocin receptor agonists](/source/Oxytocin_receptor_agonist) have also been developed.[25][26]

### Agonists

Main article: [Oxytocin receptor agonist](/source/Oxytocin_receptor_agonist)

**Peptide**

- [Carbetocin](/source/Carbetocin)

- [Demoxytocin](/source/Demoxytocin)

- [Lipo-oxytocin-1](/source/Lipo-oxytocin-1)

- [Merotocin](/source/Merotocin)

- [Oxytocin](/source/Oxytocin)

**Non-peptide**

- KNX-200 (KNX200)[27][28]

- [LIT-001](/source/LIT-001) — improved [social deficits](/source/Social_deficits) in mice; non-selective over vasopressin receptors

- [TC OT 39](/source/TC_OT_39) – non-selective over vasopressin receptors

- [WAY-267,464](/source/WAY-267%2C464) – [anxiolytic](/source/Anxiolytic) in mice; possibly non-selective over vasopressin receptors[23][29][30]

### Antagonists

**Peptide**

- [Atosiban](/source/Atosiban)

- [Barusiban](/source/Barusiban)

**Non-peptide**

- [Epelsiban](/source/Epelsiban)[31]

- [L-368,899](/source/L-368%2C899) (CAS# 148927-60-0)[32][33]

- [L-371,257](/source/L-371%2C257) (CAS# 162042-44-6)[34][35] – peripherally selective (i.e. poor [blood brain barrier](/source/Blood_brain_barrier) penetration, few central effects)[36]

- [L-372,662](https://en.wikipedia.org/w/index.php?title=L-372,662&action=edit&redlink=1)

- [Nolasiban](https://en.wikipedia.org/w/index.php?title=Nolasiban&action=edit&redlink=1)[37]

- [Retosiban](/source/Retosiban) (GSK-221,149)[31]

- [SSR-126,768](https://en.wikipedia.org/w/index.php?title=SSR-126,768&action=edit&redlink=1)

- [WAY-162,720](https://en.wikipedia.org/w/index.php?title=WAY-162,720&action=edit&redlink=1) – centrally active following peripheral administration

### Positive allosteric modulators

- KNX-300/400 (KNX300/400)[27][28]

### Indirect agonists

- [KNX-100](/source/KNX-100) (KNX100; SOC-1)[38][39][40]

## References

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1. ^ [***a***](#cite_ref-Sami2026_27-0) [***b***](#cite_ref-Sami2026_27-1) Sami T (13 January 2026). ["Kinoxis and Boehringer to develop oxytocin-targeting treatments for social dysfunction in $181M deal"](https://www.bioworld.com/articles/696840-kinoxis-and-boehringer-to-develop-oxytocin-targeting-treatments-for-social-dysfunction-in-181m-deal?v=preview). *BioWorld*. Retrieved 13 January 2026.

1. ^ [***a***](#cite_ref-NIF2022_28-0) [***b***](#cite_ref-NIF2022_28-1) *Spotlight Showcases: Kinoxis Therapeutics Pty Ltd*. 5th Annual Neruoscience Innovation Forum for Business Development, Licensing & Investment 22nd–23rd March 2022, Digital Conference. March 2022. Kinoxis' lead candidate (KNX100) is being developed for the mitigation of opioid withdrawal symptoms. KNX100 has a novel, undisclosed mechanism of action and a Phase I clinical trial has commenced under a US IND. The company is also exploring other indications for its lead compound, KNX100, as promising preclinical results have been achieved in animal models of cocaine, methamphetamine, nicotine, and alcohol use disorders, as well as models of agitation and aggression. [...] Kinoxis' second series of compounds target the oxytocin receptor, through either selective partial agonism or positive allosteric modulation. The brain oxytocin system has been identified as perhaps the most important molecular target for regulating social behaviour and is therefore a major target of interest for treating a wide range of mental disorders. The development of these compounds will be focused on treating conditions that feature social dysfunction as a core symptom, such as neurodevelopmental disorders (including autism spectrum disorder), social anxiety disorder, dementia (including Alzheimer's disease), PTSD and schizophrenia. The KNX200 series of oxytocin receptor partial agonists are undergoing candidate selection stage using several pre-clinical animal disease models (Alzheimer's, PTSD, ASD) and the KNX300/400 series of oxytocin receptor positive allosteric modulators are undergoing lead optimisation.

1. **[^](#cite_ref-WO_2007050353_29-0)** Rahman Z, Resnick L, Rosenzweig-Lipson SJ, Ring RH,*"Methods of treatment using oxytocin receptor agonists"*, [US patent application 2007/0117794](http://www.google.com/patents?id=3G2iAAAAEBAJ), published 2007-05-24 , assigned to Wyeth Corp

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## External links

Wikimedia Commons has media related to [Oxytocin receptors](https://commons.wikimedia.org/wiki/Category:Oxytocin_receptors).

- [Oxytocin+receptor](https://meshb.nlm.nih.gov/record/ui?name=Oxytocin+receptor) at the U.S. National Library of Medicine [Medical Subject Headings](/source/Medical_Subject_Headings) (MeSH)

- ["Symbol Report: OXTR"](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/8529). HUGO Gene Nomenclature Committee.

- ["Vasopressin and Oxytocin Receptors: OT"](http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2966). *IUPHAR Database of Receptors and Ion Channels*. International Union of Basic and Clinical Pharmacology.

*This article incorporates text from the [United States National Library of Medicine](/source/United_States_National_Library_of_Medicine), which is in the [public domain](/source/Public_domain).*

v t e Cell surface receptor: G protein-coupled receptors Class A: Rhodopsin-like Neurotransmitter Adrenergic α1 A B D α2 A B C β1 β2 β3 Purinergic Adenosine A1 A2A A2B A3 P2Y 1 2 4 5 6 8 9 10 11 12 13 14 Serotonin (all but 5-HT3) 5-HT1 A B D E F 5-HT2 A B C 5-HT 4 5A 6 7 Other Acetylcholine M1 M2 M3 M4 M5 Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin 1A 1B 1C TAAR 1 2 5 6 8 9 Metabolites and signaling molecules Eicosanoid CysLT 1 2 LTB4 1 2 FPRL1 OXE Prostaglandin DP 1 2 EP 1 2 3 4 FP Prostacyclin Thromboxane Other Bile acid Cannabinoid CB1 CB2 GPR 18 55 119 EBI2 Estrogen Free fatty acid 1 2 3 4 Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid 1 2 3 4 5 6 Lysophospholipid 1 2 3 4 5 6 7 8 Oxoglutarate PAF Sphingosine-1-phosphate 1 2 3 4 5 Succinate Peptide Neuropeptide B/W 1 2 FF 1 2 S Y 1 2 4 5 Neuromedin B U 1 2 Neurotensin 1 2 Other Anaphylatoxin C3a C5a 1 2 Angiotensin 1 2 Apelin Bombesin BRS3 GRPR NMBR Bradykinin B1 B2 Chemerin 1 2 Chemokine Cholecystokinin A B Endothelin A B Formyl peptide 1 2 3 FSH Galanin 1 2 3 Gonadotropin-releasing hormone 1 2 Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS 1 1L D E F G X1 X2 X3 X4 Melanocortin 1 2 3 4 5 MCHR 1 2 Motilin Opioid Delta Kappa Mu Nociceptin & Zeta, but not Sigma Orexin 1 2 Oxytocin Prokineticin 1 2 Prolactin-releasing peptide Relaxin 1 2 3 4 Somatostatin 1 2 3 4 5 Tachykinin 1 2 3 Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin 1A 1B 2 Miscellaneous Taste, bitter TAS2R 1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor type 1 Orphan GPR 3 4 6 12 15 17 18 19 20 21 22 26 27 31 32 33 34 35 37 39 42 45 50 52 55 61 62 63 65 68 75 78 82 83 84 85 87 88 101 103 109A 119 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183 Other Adrenomedullin Olfactory Opsin 3 4 5 1LW 1MW 1SW RGR RRH Protease-activated 1 2 3 4 SREB 1 2 3 Class B: Secretin-like Adhesion ADGRB Brain-specific angiogenesis inhibitor 1 2 3 ADGRC Cadherin 1 2 3 ADGRE EMR 1 2 3 CD97 ADGRG 1 2 3 4 5 6 7 ADGRL Latrophilin 1 2 3 ELTD1 Orphan GPR 56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157 Other Calcitonin CALCRL Corticotropin-releasing hormone 1 2 Glucagon GR GIPR GLP1R GLP2R Growth-hormone-releasing hormone PACAPR1 GPR Methuselah-like proteins Parathyroid hormone 1 2 Secretin Vasoactive intestinal peptide 1 2 Class C: Metabotropic glutamate / pheromone Taste, sweet TAS1R 1 2 3 Vomeronasal receptor, type 2 Other Calcium-sensing receptor GABAB 1 2 Glutamate receptor Metabotropic glutamate 1 2 3 4 5 6 7 8 GPRC6A GPR 156 158 179 RAIG 1 2 3 4 Class F: Frizzled & Smoothened Frizzled Frizzled 1 2 3 4 5 6 7 8 9 10 Smoothened Smoothened Category Commons

v t e Neuropeptide receptors G protein-coupled receptor Hormone receptors Hypothalamic CRH FSH LHRH TRH Somatostatin Pituitary Vasopressin 1A 1B 2 Oxytocin LHCG TSH Other Atrial natriuretic factor NPR3 Calcitonin Cholecystokinin A B VIP Opioid receptors Delta Kappa Mu Nociceptin Other neuropeptide receptors Angiotensin Bradykinin B1 B2 Tachykinin TACR1 Calcitonin gene-related peptide Galanin GPCR neuropeptide B/W FF S Y Neurotensin Type I cytokine receptor GH Prolactin Enzyme-linked receptor Atrial natriuretic factor NPR1 NPR2 Other Sigma 1 2

v t e Oxytocin and vasopressin receptor modulators Oxytocin Agonists: Peptide: Aspartocin Carbetocin Cargutocin Demoxytocin Lipo-oxytocin-1 Merotocin Nacartocin Oxytocin PF-06478939 PF-06655075 (PF1) TGOT Vasotocin (argiprestocin); Non-peptide: CA7 KNX-200 (KNX200) LIT-001 LIT-002 TC OT 39 WAY-267464 WJ0679; Unknown: NP-1031 Antagonists: Peptide: Atosiban Tocinoic acid; Non-peptide: Barusiban Cligosiban Epelsiban Erlosiban L-368,899 L-371,257 L-372,662 Nolasiban Retosiban SSR-126768 WAY-162720 Positive allosteric modulators: KNX-300/400 (KNX300/400) Indirect agonists: Non-peptide: KNX-100 (KNX100; SOC-1) KNX-101 (KNX101) Catabolism inhibitors: Amastatin Bestatin (ubenimex) EDTA L-Methionine Leupeptin o-Phenanthroline Phosphoramidon Puromycin Vasopressin V1A Agonists: Felypressin Lypressin Ornipressin Selepressin Terlipressin Vasopressin (argipressin) Vasotocin (argiprestocin) Antagonists: Atosiban Balovaptan Conivaptan FR-218944 JNJ-17079166 JNJ-17308616 LIT-001 LY-307174 NMRA-511 NTX-1472 (RO-6953958) PF-184563 Relcovaptan RG7713 SRX246 SRX251 TC OT 39 WAY-267464 YM-218 YM-471 YM-35471 V1B Agonists: Desmopressin Felypressin Lypressin Ornipressin Terlipressin Vasopressin (argipressin) Vasotocin (argiprestocin) Antagonists: ABT-436 ABT-558 Brezivaptan Nelivaptan (SSR-149415, NB-415, BH-200) ORG-52186 (SCH-740935) TASP-0233278 TASP-0390325 Ligands: TASP-699 V2 Agonists: Desmopressin Felypressin LIT-001 LIT-002 Lypressin Ornipressin TC OT 39 Terlipressin Vasopressin (argipressin) Vasotocin (argiprestocin) Antagonists: Conivaptan JNJ-17079166 Lixivaptan Mozavaptan RWJ-351647 Satavaptan Tolvaptan YM-471 YM-35471 Unsorted Antagonists: Balovaptan Ribuvaptan RWJ-339489 VMAX-367 VMAX-372 VMAX-382 YM-222546 Other inhibitors: Demeclocycline Lithium (lithium carbonate) Others Carrier proteins: Neurophysin (I, II)

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Adapted from the Wikipedia article [Oxytocin receptor](https://en.wikipedia.org/wiki/Oxytocin_receptor) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Oxytocin_receptor?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.