N-Nitroso metoprolol is a genotoxic derivative of metoprolol .1,2 It induces DNA fragmentation in rat hepatocytes when used at concentrations ranging from 0.1 to 1 mM.1 In vivo, N-nitroso metoprolol (1,000 mg/kg) induces micronucleation of rat hepatocytes but not erythrocytes from the bone marrow or spleen.
1.Robbiano, L., Martelli, A., Allavena, A., et al.Formation of the N-nitroso derivatives of six β-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytesCancer Res.51(9)2273-2279(1991) 2.Martelli, A., Allavena, A., Sottofattori, E., et al.Low clastogenic activity in vivo of the N-nitroso derivatives of 5 β-adrenergic-blocking drugs proved to be potent genotoxins in vitroToxicol. Lett.73(3)185-191(1994)