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

Aims The 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 methods To 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, 800 mg/kg) and through ad libitum oral ingestion of glycinamide solution (40 mg/ml) following a 24 h period of water deprivation. Key findings Glycinamide exerted a significant analgesic effect on VT when injected i.p. at doses of 400 or 800 mg/kg. Analgesia occurred 10-20 min post-injection and persisted approx 45 min. At the high dose level, glycinamide exerted a weaker and more delayed effect on TFL than on the VT test. I.p. injection of 800 mg/kg glycinamide inhibited vocalizations induced by the application of suprathreshold tail shocks (30% above threshold) with a latency of approx 3 min and duration of approx 1 h. The volume of a glycinamide solution (40 mg/ml) ingested by rats deprived of water for 24 h was positively correlated with the degree of analgesia in the VT test. Values between 100 and 200 mg glycinamide exerted clear analgesic responses. Significance Thus, 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.