(-)-P7C3-S243

(-)-P7C3-S243 is an orally active neuroprotective agent capable of crossing the blood-brain barrier. It binds to the μ-opioid receptor (Opioid Receptor) and TSPO. This compound inhibits premature apoptosis in newborn hippocampal neurons, protects mature substantia nigra dopaminergic neurons, enhances neuronal survival, and prevents cognitive impairment. Additionally, (-)-P7C3-S243 improves depressive-like behavior in rat models and is applicable in research related to Parkinson's and Alzheimer's diseases.

(−)-P7C3-S243 (Compound 15) exhibits mild in vitro inhibition of CYP1A2 (IC 50 = 20 μM) and CYP2C19 (IC 50 = 1.9 μM), while showing no inhibitory effects on various other tested CYP isoforms. Additionally, (−)-P7C3-S243 binds in vitro to the μ-opioid receptor (IC 50 = 8.2 μM) and TSPO (IC 50 = 0.35 μM), but does not interact with most other tested neuronal receptors and channels.

The compound (−)-P7C3-S243, administered at 10 μM (12 μL/day) or 0.1-10 mg/kg/day intraventricularly (i.c.v.) or intraperitoneally (i.p.) twice daily for 7 days, doubles the number of surviving newborn hippocampal neurons in mice under deprived conditions, enhancing neuron survival [1]. Additionally, (−)-P7C3-S243 administered intraperitoneally at 1-10 mg/kg twice daily for 21 consecutive days exhibits a dose-dependent protective effect on mature dopaminergic neurons in the substantia nigra of MPTP-treated mice. Moreover, a 10-day intraperitoneal administration of (−)-P7C3-S243 at 10 mg/kg significantly enhances hippocampal neurogenesis in postnatal TgF344-AD rats, safeguarding them from early depressive-like behaviors and late-stage cognitive impairments, while reducing neurodegeneration and neuronal loss. It also ameliorates age-related depressive-like behaviors in wild-type rats.