Oseltamivir Blocks Human Neuronal Nicotinic Acetylcholine Receptor-Mediated Currents

The effects of oseltamivir, a neuraminidase inhibitor, were tested on the function of neuronal nicotinic acetylcholine receptors (nAChRs) in a neuroblastoma cell line IMR32 derived from human peripheral neurons and on recombinant human 34 nAChRs expressed in HEK cells. IMR32 cells predominately express 34 nAChRs. Nicotine (nic, 30m)-evoked currents recorded at -90mV in IMR32 cells using the whole-cell patch clamp technique were reversibly blocked by oseltamivir in a concentration-dependent manner. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) at 30m had little effect on the nic-evoked currents. Oseltamivir also blocked nic-evoked currents derived from HEK cells with recombinant 34 nAChRs. This blockade was voltage-dependent with 10, 30 and 100 m oseltamivir inhibiting similar to 50% at -100, -60 and -40mV, respectively. Non-inactivating currents in IMR32 cells and in HEK cells with 34 nAChRs, which were evoked by an endogenous nicotinic agonist, ACh (5m), were reversibly blocked by oseltamivir. These data demonstrate that oseltamivir blocks nAChRs, presumably via binding to a site in the channel pore.