Salbutamol and Formoterol Attenuate Okadaic Acid-Induced Cytotoxicity in Undifferentiated PC-12 Cells: Evidence for a β2-Adrenergic Receptor-Independent Protective Component

β2-adrenergic receptor (β2-AR) agonists have been implicated in neuroprotection, yet their mechanisms remain obscure. We examined whether salbutamol (SA, short-acting) or formoterol (FO, long-acting) protect PC-12 cells from okadaic acid (OA), and evaluated receptor dependence, antioxidant capacity, and apoptotic signaling. Viability was quantified with crystal violet and MTT assays. OA reduced viability to approximately 60%, and SA or FO (0.1–10 µM) improved survival, which reached 76–83% at 10 µM (p < 0.05). β2-AR blockage with ICI-118,551, and ADRB2 mRNA knockdown did not abolish protection by FO or SA, suggesting a possible β2-AR-independent protective component. However, as knockdown was not confirmed at the protein level and signaling was not directly assessed, the evidence remains provisional. FO, but not SA, exhibited direct antioxidant activity in the DPPH assay, but both at 50 μΜ lowered H2O2-induced intracellular reactive oxygen species (from 167.9% to baseline, p < 0.05). Both compounds reduced the OA-induced expression of selected pro-apoptotic transcripts, although these mRNA data do not establish the functional inhibition of apoptosis. FO reduced fold change relative to untreated control from 5.8 to 2.6 for Bax, and 6.4 to 3.4 for Bak, whereas SA achieved a significant reduction only for Bax, from 5.8 to 4.4. Taken together, SA and FO offer a partial protection to PC-12 cells from OA cytotoxicity through pathways suggesting a β2-AR-independent protective component, with FO showing additional antioxidant properties and a reduced expression of selected pro-apoptotic transcripts. These findings provide preliminary evidence that select β2 agonists may exert cytoprotective effects that are consistent with, but do not establish, a receptor-independent component. These findings warrant further protein-level and functional validation.