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

Abstract

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. 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 [ED(20)], ED(50), and ED(80)). Lidocaine, a frequently used local anesthetic, was used as control. 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). 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.