N-Oleoyldopamine

N-Oleoyldopamine (OLDA) is an orally active TRPV1 activator and 5-LOX inhibitor with blood-brain barrier permeability. N-Oleoyldopamine excites histaminergic neurons in the tuberomammillary nucleus via a dopamine receptor mechanism, a process independent of TRPV1 and cannabinoid receptors. On one hand, N-Oleoyldopamine promotes the release of insulin and glucose-dependent insulinotropic polypeptide through a GPR119-dependent pathway to improve glucose tolerance; on the other hand, N-Oleoyldopamine improves left ventricular function and reduces myocardial infarction size by triggering the release of substance P and calcitonin gene-related peptide. N-Oleoyldopamine is used in studies related to glycemic abnormalities and myocardial ischemia-reperfusion injury^[1][2][3]. In Vitro:N-Oleoyldopamine activates HEK293 cells transfected with human GPR119, thereby increasing cAMP accumulation, with an EC₅₀ of 3.2 μM^[2].
N-Oleoyldopamine (50 μM; 1 h) significantly stimulates insulin secretion in HIT-T15 cells in a GPR119-dependent and TRPV1-independent manner^[2].
N-Oleoyldopamine (3-100 μM) dose-dependently stimulates cAMP accumulation and insulin release in RIN-5F cells transfected with human GPR119, while no such effect is observed in control RIN-5F cells that do not express GPR119^[2]. In Vivo:OLDA (100 mg/kg; p.o.; single dose) acutely elevates plasma GIP levels by ~2-fold and significantly improves oral glucose tolerance in wild-type C57Bl/6 male mice in a GPR119-dependent manner^[2].
OLDA (100 mg/kg; p.o.; single dose) fails to alter GIP release or glucose tolerance in GPR119-deficient mice^[2].