Sameridine - intrathecal injection in the rat - Morphometric and morphologic analysis after chronic administration and effects on spinal cord blood flow

Background: Sameridine is a type of compound with both local anaesthetic an d analgesic effects with the clinical intention to be used intrathecally (I T) in order to provide both surgical anaesthesia and prolonged postoperativ e analgesia. Before new drugs are introduced for clinical use, they must be tested for potential toxic effects. Methods: In the present study sameridine (5 or 10 mg/ml), bupivacaine (5 mg /ml) or saline (9 mg/ml) was injected intrathecally in rats twice, daily (a t 07:00 and 19:00), 5 days a week for 2 weeks. Thereafter, the rats were an aesthetised, perfused and the spinal cords were prepared for microscopic in vestigation. A morphologic method, using light and electron microscopic exa mination of the cross-section of the spinal cord, was combined with a quant itative morphometric analysis of the number and size of neuronal cells in t he dorsal horn as a sensitive indicator of neurotoxicity. Using the laser-D oppler flowmetry technique, the effects of saline and sameridine (1, 5 and 10 mg/ml) on spinal cord blood flow (SCBF) was studied. Results: No signs of neurotoxicity could be seen in any of the animals and no significant differences were seen when comparing the cell number or cell sizes in the groups injected with sameridine, bupivacaine or saline. After IT administration of 10 mg/ml sameridine a significant, short-lasting, dec rease in SCBF (72% of pre-drug value) was seen. Conclusion: In conclusion, our studies do not show any signs of neurotoxic effects of IT administration of sameridine in the rat. A transient decrease in SCBF was noted after IT injection of sameridine 10 mg/ml.