Co-administration of memantine with epinephrine produces a marked peripheral action in intensifying and prolonging analgesia in response to local skin pinprick in rats

The purpose of this study was to examine the effect of epinephrine as adjuvant for memantine or lidocaine as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we evaluated the effects of adding epinephrine to memantine or lidocaine on infiltrative cutaneous analgesia. Lidocaine, a known local anesthetic, was used as control. We found that epinephrine, memantine, and lidocaine produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. On a 50% effective dose (ED50) basis, the relative potencies were epinephrine [0.012 (0.006-0.020) μmol] > memantine [4.010 (3.311-4.988) μmol] > lidocaine [6.177 (5.333-7.218) μmol] (P < 0.05 for each comparison). Mixtures of epinephrine (2.7 nmol or 13.7 nmol) with drugs (memantine or lidocaine) at ED50 or ED95, respectively, enhanced the potency and prolonged the duration of action on infiltrative cutaneous analgesia. Intraperitoneal injection of co-administration of drugs (memantine or lidocaine) at ED95 with epinephrine (13.7 nmol) produced no cutaneous analgesia (data not shown). Epinephrine, memantine, and lidocaine were shown to have local anesthetic effects as infiltrative cutaneous analgesia. Epinephrine increased the duration and potency of memantine and lidocaine as an infiltrative anesthetic.