Glycinamide, a glycine pro-drug, induces antinociception by intraperitoneal or oral ingestion in ovariectomized rats

Abstract

AimsThe effect of i.p. injection or oral ingestion of glycinamide, a glycine pro-drug, on two tests for nociception was assessed in ovariectomized Sprague Dawley rats. Main methodsTo explore the potential analgesic effect of glycinamide the vocalization threshold to tail shock (VT) and the tail flick latency (TFL) were used. Glycinamide was administered both through the intraperitoneal route (doses 0, 25, 100, 400, 800mg/kg) and through ad libitum oral ingestion of glycinamide solution (40mg/ml) following a 24h period of water deprivation. Key findingsGlycinamide exerted a significant analgesic effect on VT when injected i.p. at doses of 400 or 800mg/kg. Analgesia occurred 10–20min post-injection and persisted approx 45min. At the high dose level, glycinamide exerted a weaker and more delayed effect on TFL than on the VT test. I.p. injection of 800mg/kg glycinamide inhibited vocalizations induced by the application of suprathreshold tail shocks (30% above threshold) with a latency of approx 3min and duration of approx 1h. The volume of a glycinamide solution (40mg/ml) ingested by rats deprived of water for 24h was positively correlated with the degree of analgesia in the VT test. Values between 100 and 200mg glycinamide exerted clear analgesic responses. SignificanceThus, glycinamide, either by systemic or oral routes, exerts a clear analgesic effect in the VT test of nociception and a much weaker action in the TFL test. This effect is probably due to the conversion of glycinamide to glycine in the brain.