The local anesthetic effect of memantine on infiltrative cutaneous analgesia in the rat

Background: Memantine blocks N-methyl-D-aspartate receptors and the Na current, one principal mechanism of local anesthesia. Until now, no study mentioned that memantine had a local anesthetic effect, and therefore we investigated the local anesthetic effect of memantine. Methods: After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the cutaneous analgesic effect of memantine, lidocaine, and dizocilpine (MK-801) in rats. The dose-dependent response of memantine on cutaneous analgesia was compared with lidocaine and MK-801 in rats. The duration of action for each drug was evaluated and compared on an equipotent basis (20% effective dose [ED20], ED50, and ED80). Lidocaine, a frequently used local anesthetic, was used as control. Results: We demonstrated that memantine, lidocaine, and MK-801 produced dose-dependent local anesthetic effects as infiltrative cutaneous analgesia. The relative potency was MK-801 (10.4 [9.7-11.1]) > memantine (17.6 [15.2-20.4]) > lidocaine (25.9 [23.8-28.1 ]) (P < 0.01). On an equipotent basis, memantine showed longer duration than lidocaine (P = 0.012) and MK-801 (P = 0.008). Coadministration of memantine (13.3 μmol/kg) and MK-801 (1.3 μmol/kg) produced greater blockade and duration than memantine (13.3 μmol/kg) or MK-801 (1.3 μmol/kg) alone. Neither local injection of saline nor intraperitoneal administration of a large dose of memantine, lidocaine, or MK-801 produced cutaneous analgesia (data not shown). Conclusions: This study indicated that memantine is less potent than MK-801, and that memantine elicits longer analgesic duration than both lidocaine and MK-801. When combined with MK-801, memantine demonstrates a synergetic effect of cutaneous analgesia. We conclude that memantine produces better local analgesia than lidocaine and that N-methyl-D-aspartate receptors also contribute to the analgesic effect of memantine.