Local anesthetics block not only the Na+ but also the K+ and Ca2+ channels in the mammalian neurons. It is well known that lidocaine has neuroprotective actions against the ischemic insult of neurons in the central nervous system. In order to elucidate how other local anesthetics as well as lidocaine show the neuroprotective effects against in vitro ischemic insult, intracellular recordings were made from CA1 pyramidal neurons in rat hippocampal slices. Superfusion with the medium deprived of oxygen and glucose (in vitro ischemia) produced a rapid depolarization after 5min of exposure. When the normal medium was immediately reintroduced after the rapid depolarization, the membrane depolarized further (persistent depolarization), the neurons showed no functional recovery. Pretreatment with tetracaine, bupivacaine, procaine, lidocaine, mepivacaine, or dibucaine (10 or 300μM) prolonged the latency of the rapid depolarization, and most of the drugs partially restored the membrane potential toward the pre-exposure level after the reintroduction. Judging from the neuroprotective actions such as the prolongation and the potential recovery by these drugs, lidocaine, bupivacaine, and dibucaine are candidates for the therapeutic use against the ischemic insult. Suppression of the regenerative Na+ conductance is somehow involved in the neuroprotective actions of local anesthetics. [Copyright &y& Elsevier]