Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats

Abstract

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade.

Spinal sensory and motor blockade by intrathecal doxylamine and triprolidine in rats

“…Nociception was regarding vocalization or the withdrawal reflex provoking by nipping the two hind paws (lateral metatarsus), the mid‐tail (dorsal area) and the skin fold of the rat's back around the tail. Nociceptive blockade was scored as 4 (100% MPE or absent), 3 (75% MPE), 2 (50% MPE), 1 (25% MPE) and 0 (0% MPE or normal) …”

“…Nociceptive blockade was scored as 4 (100% MPE or absent), 3 (75% MPE), 2 (50% MPE), 1 (25% MPE) and 0 (0% MPE or normal). [26,27] The AUCs, full recovery time and ED 50…”

Naloxone prolongs cutaneous nociceptive block by lidocaine in rats

“…The percentage of maximum possible effect (%MPE) was defined as the maximum blockade in the time course of drugꞌs action. Furthermore, the area under the curve (AUC) of drug action was calculated by Kinetica version 2.0.1 (InnaPhase Corporation, Philadelphia, PA) . The dose‐related curves were obtained from the %MPE of each dose of each drug after animals were injected with different doses of each drug subcutaneously.…”

Intrathecal pramoxine causes long-lasting spinal sensory and motor block in rats

“…Proprioception was tested through the postural reactions ('tactile placing' or 'hopping') and resting posture and was scored as 3 (normal or 0%MPE), 2 (slightly defective), 1 (severely defective) and 0 (fully defective or 100%MPE). [19,20] The animal was moved laterally, which normally caused a rapid hopping response, through lifting the front half of the animal off the ground and lifting a hindlimb at a time off the ground so that the animal was standing on just another limb, with the weight-bearing limb in the direction of movement to prevent the animal from falling.…”