Oxytocin Receptor Antagonist

Rationale for use of centrally acting oxytocin receptor antagonists to treat Premature Ejaculation

3 D molecule representationPreclinical and clinical studies indicate that oxytocin is an important transmitter in the central nervous system facilitating ejaculation.

In rats, copulatory behavior / ejaculation activates oxytocinergic neurons in the brain.  Oxytocin shortens time to ejaculation when infused directly into the cerebral ventricles.  In oxytocin receptor knockout mice, there is a decreased incidence of ejaculation and a higher stimulatory threshold required to induce ejaculation compared with wild type mice.

Male anatomy of human brain in x-ray viewIn men, circulating levels of oxytocin increase during sexual stimulation and arousal, and peak during ejaculation.  As in rodents, oxytocin facilitates ejaculation with case reports of the treatment of male anorgasmia by intranasal dosing of oxytocin. Previous pre-clinical and clinical studies with epelsiban and various peptide oxytocin receptor antagonists, have demonstrated that non-CNS penetrant oxytocin receptor antagonists show little effect on ejaculation when given systemically. However, rodent studies show that they can delay or prevent ejaculation when injected close to the lower thoracic and lower lumbar spinal cord or when injected directly into the cerebral ventricle strongly supporting the hypothesis that a centrally acting oxytocin receptor antagonist has the potential to treat premature ejaculation. Ixchelsis is developing IX-01, a small molecule orally delivered oxytocin receptor antagonist that has demonstrated good CNS penetration in preclinical studies.  This compound is the only CNS penetrant oxytocin receptor antagonist in clinical development.


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