{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:25:10Z","timestamp":1787117110545,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) remains a major neurodegenerative disorder with limited therapeutic options. Several\n                    <jats:italic>in vivo<\/jats:italic>\n                    animal studies using different experimental PD models have shown that progesterone (P4) may exert neuroprotective effects; however, the exact cellular and molecular mechanisms, including the receptors mediating these actions of P4, have not been investigated. A recent study from the laboratory of Peter Thomas demonstrated that the selective membrane progesterone receptor \u03b1 (mPR\u03b1\/PAQR7) agonist Org OD 02-0 (10-ethenyl-19-norprogesterone) exhibits neuroprotective effects in a human PD cell model, identifying mPR\u03b1 as a promising target for the development of therapeutic strategies for PD prevention and management. However, the blood-brain barrier (BBB) penetration and\n                    <jats:italic>in vivo<\/jats:italic>\n                    pharmacokinetics of Org OD 02\u20130 have not yet been examined. Therefore, the aim of the present pilot study was to investigate the BBB penetration and tissue distribution of Org OD 02\u20130 following systemic administration in rats. To achieve this, we first developed a sensitive high-performance liquid chromatography-coupled mass spectrometry method for the detection and quantification of Org OD 02\u20130 in rat tissues. Using this method, we investigated the distribution of Org OD 02\u20130 in male Wistar rats following subcutaneous administration (2.6 mg\/kg). Org OD 02\u20130 was detectable in all examined tissues, showing higher concentrations in the brain (frontal lobe) and kidney and lower levels in plasma and liver at 1, 3, 6, and 12\u00a0h post-injection. The concentration data suggested differential tissue distribution and potential preferential accumulation in the kidneys. Importantly, our results demonstrate, for the first time, that Org OD 02\u20130 crosses the BBB and reaches pharmacologically relevant concentrations in the central nervous system following systemic administration, supporting its potential as a candidate for PD therapy. Based on these data,\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies in rat PD models are warranted to further evaluate the therapeutic efficacy of Org OD 02-0.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1870020","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:39:09Z","timestamp":1787114349000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood-brain barrier penetration and tissue distribution of the selective membrane progesterone receptor \u03b1 (mPR\u03b1\/PAQR7) agonist Org OD 02-0"],"prefix":"10.3389","volume":"17","author":[{"given":"L\u00e1szl\u00f3 \u00c1kos","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Anatomy, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]},{"name":"Research Group for Mood Disorders, Centre for Neuroscience, Medical School, 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