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 and analgesic effects with the clinical intention to be used intrathecally (i.t.) in order to provide both surgical anaesthesia and prolonged postoperative 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 (at 07:00 and 19:00), 5 days a week for 2 weeks. Thereafter, the rats were anaesthetised, perfused and the spinal cords were prepared for microscopic investigation. A morphologic method, using light and electron microscopic examination of the cross-section of the spinal cord, was combined with a quantitative morphometric analysis of the number and size of neuronal cells in the dorsal horn as a sensitive indicator of neurotoxicity. Using the laser-Doppler 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 i.t. administration of 10 mg/ml sameridine a significant, short-lasting, decrease in SCBF (72% of pre-drug value) was seen.


CONCLUSIONS
In conclusion, our studies do not show any signs of neurotoxic effects of i.t. administration of sameridine in the rat. A transient decrease in SCBF was noted after i.t. injection of sameridine 10 mg/ml.
Karlsten
R
R
Department of Anaesthesiology, University Hospital, Uppsala, Sweden.
Gordh
T
T
Kristensen
J D
JD
Ask
A L
AL
Svensson
B A
BA
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D007278:Injections, Spinal; D017078:Laser-Doppler Flowmetry; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D016037:Single-Blind Method; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology
D000700:Analgesics; D000779:Anesthetics, Local; D010880:Piperidines; C113809:sameridine; D002045:Bupivacaine