The anticonvulsant remacemide and its metabolite AR-R12495AA attenuate spinal synaptic transmission and carrageenan-induced inflammation in the young rat

Abstract

The effects of the anticonvulsants remacemide [(±)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamide hydrochloride] and its des -glycinated metabolite AR-R12495AA [(±)-1-methyl-1,2-diphenylethylamine- monohydrochloride] on primary afferent-induced synaptic transmission and frequency-dependent summation of synaptic potentials were assessed in the young rat spinal cord in vitro. Behavioural studies in the rat determined the effects of these anticonvulsant compounds in the carrageenan model of inflammation. Recordings of the extracellular dorsal root-evoked ventral root potential (DR-VRP) revealed a significant reduction of the duration andt1 -2decay of the long latency, slow DR-VRP by remacemide (50 and 100 μM) and AR-R12495AA (25, 50 and 100 mM). The short-latency, fast monosynaptic DR-VRP peak was reduced by only the highest concentration of AR-R12495AA (100 μM). In intracellular dorsal root-evoked excitatory postsynaptic potentials (DR-EPSPs) of single ventral horn neurons, AR-R12495AA (100 μM) attenuated the time course of the long-latency (slow) EPSP. Frequency-dependent (0.5–2.0 Hz) summation of dorsal root-evoked synaptic events (recorded extracellularly as the cumulative ventral root depolarization (CVRD), and intracellularly as wind-up) was attenuated by remacemide (100 μM) and AR-R12495AA (50 and 100 μM). Pre-treatment with intra-peritoneal injection of 75 mg/kg of remacemide or AR-R12495AA caused a significant reduction of carrageenan-induced mechanical hyperalgesia and oedema. These electrophysiological and behavioural data provide evidence that remacemide and AR-R12495AA may also possess analgesic and anti-inflammatory activity. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain