oxytocin intranasal (TNX-1900) / Tonix - LARVOL DELTA

Evaluating Intranasal Oxytocin (TNX-1900) for Pain Relief and Recovery After Pituitary Surgery (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Pain

Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Elizabeth Austen Lawson | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date

Overexpression of regenerating islet-derived type 4 isoform 2 increases colorectal cancer cell proliferation. (PubMed, Biochem Biophys Rep) - "Real-time polymerase chain reaction (RT-qPCR) revealed higher REG4 isoform 2 expression in colon cancer cell lines (DLD-1, HCT116, and HT29) than in normal tissue-derived cell lines (HDLECs, HME1, HUVECs, and TIG114), similar to that of REG4 isoform 1...Furthermore, in a subset of patients, the expression of this isoform in CRC tissues was higher than that in the adjacent normal tissues in human specimens. These results suggest that REG4 isoform 2, similar to isoform 1, is associated with enhanced proliferative properties of colon cancer cells and highlight the need for further investigation of isoform 2 in future studies."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Vasopressin 1A and 1B receptor-mediated antinociception in a mouse model of cortical spreading depolarization. (PubMed, Pain) - "We examined the effect of selective vasopressin 1A receptor antagonist relcovaptan and vasopressin 1B receptor antagonist nelivaptan on SD-induced migraine-relevant behavior...However, there was no effect of either drug on opto-SD-induced grimace, photosensitivity, or locomotion. These data are consistent with an analgesic effect of endogenous vasopressinergic receptor activation in a mouse model of migraine."

Journal • Preclinical • CNS Disorders • Migraine • Mood Disorders • Pain • Psychiatry • THY1

Tonix Pharmaceuticals Announces First Participant Dosed in Phase 1 Investigator-Initiated Pharmacodynamic Study of TNX-1900 (Intranasal Potentiated Oxytocin) to Assess Potential for Treating Migraine and Craniofacial Pain (GlobeNewswire) - "TNX-1900 will be studied in the trigeminal neurovascular reactivity model, by measuring the forehead skin blood flow response to capsaicin and electrical stimulation by Laser Speckle Contrast Imaging (LSCI)."

Trial status • Migraine

Intranasal Drug Delivery in Neuropharmacology: Advances in Brain-Targeted Therapies and Bioethical Challenges. (PubMed, Biomedicines) - "The ease of intranasal administration introduces profound bioethical dilemmas regarding neuroenhancement, authenticity, and informed consent in vulnerable populations. The current literature concludes that realizing the full potential of nose-to-brain (N2B) therapy requires a commitment to precision medicine, utilizing specialized delivery devices and objective biomarkers to ensure safe and equitable clinical application."

Journal • Review • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders

Targeting the brain through the nose: Advances in polymeric nanoparticle delivery for schizophrenia. (PubMed, Neuropeptides) - "Future research must prioritize nanoparticle design optimization for enhanced mucoadhesion and mucopenetration, improved brain targeting through ligand engineering, validation in physiologically relevant models including ex vivo human tissue, comprehensive chronic toxicity evaluation, and alignment with evolving regulatory frameworks. Intranasal PNPs represent a paradigm shift in treating schizophrenia and other neuropsychiatric disorders, offering a non-invasive, patient-friendly, and potentially more effective therapeutic modality."

Journal • Review • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia

Hyperprolactinemia and migraine-like headache: A case report and literature review (EHF-EHC 2025) - "She was treated with bromocriptine for three months, achieving complete headache resolution...Repeat MRI showed a pituitary microadenoma, and cabergoline was reinitiated, with significant headache improvement...Eletriptan was prescribed for acute attacks... This case supports the role of PRL in migraine-like headaches via neuromodulatory effects, independent of tumor mass. PRL receptors in trigeminal pathways suggest a sensitization mechanism. Dopamine agonists may relieve symptoms, even without tumor shrinkage, indicating a hormonal component."

Case report • Clinical • Review • CNS Disorders • Endocrine Disorders • Gynecology • Migraine • Pain

First-in-human intranasal [13N]oxytocin PET: evaluation of feasibility, biodistribution, and radiation dosimetry. (PubMed, EJNMMI Res) - P1 | "Intranasal [13N]oxytocin administration results in rapid and substantial nasal cavity uptake and detectable, but variable, tracer distribution to trigeminal and brain regions. While this technique offers insight into intranasal peptide delivery, limitations related to variable absorption, short half-life, and image co-registration must be addressed. Accordingly, [13N]oxytocin is not presently well suited for central nervous system receptor imaging via intranasal administration. Peripheral receptor imaging after intravenous administration may still be feasible, and further optimisation of tracer chemistry, administration protocols, and imaging strategies is warranted."

First-in-human • Journal • P1 data • Inflammation • Otorhinolaryngology • Pain • Psychiatry

Bifurcated projections from the trigeminal ganglion cells to the infraorbital nerve and transverse sinus: correlation with the oxytocin receptor and CGRP. (Neuroscience 2025) - "These findings suggest that individual TG cells can project through both the V1 and V2 branches, with OTR present in meningeal structures related to headache nociception. This supports earlier studies highlighting OTR's role in inhibiting CGRPergic nerve activity."

CNS Disorders • Migraine

Bifurcated projections from the trigeminal ganglion cells to the transverse sinus and infraorbital nerve in the rat: correlation with the oxytocin receptor and CGRP. (PubMed, J Headache Pain) - "To the best of our knowledge, these data support the contention that some TG cells send bifurcated neuronal projections through the V1 and V2 branches. Furthermore, these data reinforce previous suggestions regarding the relevance of OTR in the trigeminovascular system."

Journal • Preclinical • CNS Disorders • Migraine • Ophthalmology • Pain

Neurophysiological aspects of migraine: The role of the hypothalamus in triggering attacks (IHC 2025) - "Understanding these neurophysiological aspects is essential for developing new therapeutic approaches aimed not only at symptom relief but also at preventing attacks through neurophysiological control. References https://doi.org/10.3390/jcm14072160 https://doi.org/10.1186/s10194-024-01914-z https://doi.org/10.3390/ijms241210092 https://doi.org/10.3390/ijms242316876 https://doi.org/10.1186/s10194-025-02044-w https://doi.org/10.1080/14737175.2024.2328728"

CNS Disorders • Migraine • ADCYAP1

Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Elizabeth Austen Lawson | Not yet recruiting ➔ Recruiting

Enrollment open

A neural circuit from hypothalamic paraventricular oxytocin neurons to trigeminal nucleus caudalis GABAergic neurons modulates pain sensitization in a mouse model of chronic migraine. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - "PVN OXT neurons exert a descending facilitatory effect on GABAergic neurons in the TNC via OXT release, thereby ameliorating pain sensitization in chronic migraine."

Journal • Preclinical • CNS Disorders • Migraine • Pain • FOS • OXT

Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Elizabeth Austen Lawson | N=30 ➔ 40 | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date

STROBE: A Study of the Effects of Oxytocin in Adults With Binge-eating Disorder (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Apr 2024 ➔ Dec 2026 | Trial primary completion date: Apr 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Binge Eating Disorder • CNS Disorders

Compromised PGF2α signaling in the paraventricular hypothalamic nucleus contributes to the central sensitization of the nitroglycerin-induced chronic migraine in male mice. (PubMed, J Headache Pain) - "Targeting FP overexpression in PVN OXT neurons restored neuronal activity and ameliorated chronic migraine hyperalgesia. Overall, our study reveals a novel neural and molecular mechanism for descending modulation of trigeminal central sensitization, thereby providing a basis for treating chronic migraine."

Journal • Preclinical • CNS Disorders • Migraine • Pain

Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults. (PubMed, Br J Anaesth) - P1, P4 | "The pharmacokinetics of intravenous oxytocin are well described by a two-compartment model. The low bioavailability (<1%) and large intersubject variability in plasma oxytocin after intranasal dosing could partially explain the inconsistent reports of oxytocin efficacy in the clinical literature with this delivery method. A publicly available simulator was created to guide oxytocin dosing in future studies."

Journal • PK/PD data • Obstetrics

Neural Plasticity in Migraine Chronification. (PubMed, Eur J Neurosci) - "Still, its involvement in migraine chronification requires further studies which should include patients/animals with EM and CM. In this narrative/hypothesis paper, we review the current literature on the molecular mechanisms of CM pathogenesis and try to link them with neural plasticity and central sensitization to support the hypothesis that it is a key element in migraine chronification."

Journal • Review • CNS Disorders • Migraine • Pain

Hormonal mechanisms in the paraventricular nuclei associated with hyperalgesia in Parkinson's disease model rats. (PubMed, Biochem Biophys Res Commun) - "Contrarily, neuronal activity and blood level of AVP were unaffected by nociceptive stimuli and were significantly lower in 6-OHDA rats than in sham rats. Our findings suggest that OXT and CRH suppression is linked to hyperalgesia in PD, whereas AVP does not directly influence the observed hyperalgesia."

Journal • Preclinical • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease

Oxytocin shortens spreading depolarization-induced periorbital allodynia. (PubMed, J Headache Pain) - "These data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration."

Journal • CNS Disorders • Migraine • Pain • THY1

Changes in the analgesic mechanism of oxytocin can contribute to hyperalgesia in Parkinson's disease model rats. (PubMed, PLoS One) - "The effect of OT on hyperalgesia in 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad after intracisternal administration of OT, and the findings showed a decrease in the frequency of face rubbing and the number of c-Fos-IR cells in the Vc. In conclusion, these findings confirm presence of hyperalgesia in PD rats, potentially due to suppression of the analgesic effects of OT originating from the PVN."

Journal • Preclinical • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease • FOS

Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache? (PubMed, Pharmaceutics) - "Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin."

Journal • CNS Disorders • Inflammation • Migraine • Pain • Vascular Neurology

Oromucosal Administration of Oxytocin: The Development of 'Oxipops'. (PubMed, Pharmaceutics) - "While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use."

Journal • Review • Gastrointestinal Disorder • Mood Disorders • Pain • Psychiatry

Oxytocin analogs with enhanced craniofacial antinociceptive effects in low magnesium formulations | Poster Board #1216 (ACS-Sp 2024) - "In conclusion, intranasal R721 and related OT analogs may be candidate non-opioid analgesics for craniofacial pain. These OT analogs would not need the Mg ++ supplementation required by intranasal OT for maximal potency."

Addiction (Opioid and Alcohol) • CNS Disorders • Migraine • Pain