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

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...Dopamine agonists may relieve symptoms, even without tumor shrinkage, indicating a hormonal component. Pituitary hormones like PRL and hypothalamic peptides such as oxytocin may underlie sex differences in migraine.Endocrine evaluation is advised in refractory or atypical headache cases."

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

PREVENTION: A Study to Evaluate the Efficacy and Safety of TNX-1900 in Patients With Chronic Migraine (clinicaltrials.gov) - P2 | N=88 | Completed | Sponsor: Tonix Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Oct 2023 | Trial primary completion date: Mar 2024 ➔ Oct 2023

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

Hypothalamic paraventricular stimulation inhibits nociceptive WDR trigeminocervical complex cells via oxytocinergic transmission. (PubMed, J Neurosci) - "Furthermore, we found that oxytocin receptors are located in the primary peptidergic afferent fibers and GABAergic cells. These findings support the idea of a direct oxytocinergic pathway between the PVN and TCC and highlight the potential of oxytocin receptors as a target for migraine pain and other primary headaches."

Journal • CNS Disorders • Migraine • Pain

Active machine learning model for the dynamic simulation and growth mechanisms of carbon on metal surface. (PubMed, Nat Commun) - "Our findings accurately replicate essential subprocesses-from the preferred diffusion of carbon monomer/dimer, chain or ring formations to edge-passivated Cu-aided graphene growth and bond breaks by ion impacts. Extending our simulations to carbon deposition on metal surfaces like Cu(111), Cr(110), Ti(001), and oxygen-contaminated Cu(111), our results align closely with experimental observations, providing a practical and efficient approach for designing metallic or alloy substrates to achieve desired carbon nanostructures and explore further reaction possibilities."

Journal • Machine learning

The role of oxytocinergic transmission modulating nociception at the trigeminocervical complex (Neuroscience 2023) - "In some recorded cells, neurobiotin was injected, and using confocal microscopy, a colocalization between OTR+ and CGRP+ or OTR+ and GABA+ near the neurobiotin-filled cell was found. Together, this data suggest that oxytocinergic transmission inhibits the nociceptive activity of second-order neurons by activating OTR in CGRPergic (primary afferent fibers) or GABAergic (interneurons) cells."

CNS Disorders • Migraine • Pain

The paraventricular nucleus is required for histamine-induced itch (Neuroscience 2023) - "In this study, we tested whether chemogenetic inhibition of the PVN reduce histamine-induced scratching response. In addition, we examined which type of neuron in the PVN is associated with histamine induced itch sensation."

CNS Disorders

Oxytocinergic projection of the paraventricular nucleus hypothalamic to the trigeminocervical complex (Neuroscience 2023) - "We acknowledge Eng. Elsa Nydia Hernández Ríosfor her technical assistance with the confocal microscope."

CNS Disorders

Tonix Pharmaceuticals Completes Clinical Stage of Phase 2 PREVENTION Study of TNX-1900 for the Prevention of Migraine Headaches in Chronic Migraineurs (GlobeNewswire) - "Tonix Pharmaceuticals Holding Corp...today announced the completion of the clinical phase of the Phase 2 proof-of-concept, double-blind, randomized, placebo-controlled PREVENTION1 study of TNX-1900 (intranasal potentiated oxytocin) as a potential treatment for the prevention of migraine headaches in chronic migraineurs. A total of 88 patients were enrolled in this multi-site study in the U.S. Topline results are expected in early December 2023."

P2 data • Trial completion • CNS Disorders • Migraine • Pain