Tirilazad Mesylate

The discovery that a main neuroprotective function of MP is due to its lipid peroxidase action instead of its glucocorticoid receptor action initiated the development of steroid analogues that were mechanistically similar but did not cause associated side-effects. One such drug, tirilazad mesylate, was especially effective for recovering neural function in spinal cord injured animal models (e.g. Anderson et al. 1988; Hall 1988; Holtz & Gerdin 1991, 1992). Like MP, tirilazad mesylate inhibits lipid peroxidation and stabilizes neuronal membranes by scavenging oxygen free radicals. Tirilazad mesylate incorporates into the membrane lipid bilayer, where it restricts the movement of free oxygen radicals and prevents them from spreading to neighbouring nerves (Kavanagh & Kam 2001). In a large RCT of tirilazad mesylate used in head injured individuals, this pharmaceutical agent was shown to have no effect on recovery after six months compared to placebo (Marshall et al. 1998). Only one clinical trial has examined the effectiveness of tirilazad mesylate in acute SCI (Bracken et al. 1997), where its neuroprotective benefits were compared to those of MP.

Discussion

At present, there have been no studies comparing acute SCI individuals who received tirilazad mesylate to those who received a placebo. The only study involving this drug to date was conducted by Bracken et al. (1997) that compared a long-term and short-term dose of MP to a long term dose of tirilazad mesylate. In this study, tirilazad mesylate exhibited the same effectiveness as a short-term dose of MP and was also associated with significantly higher rates of complications (Bracken et al. 1998).

Conclusion

There is level 1b evidence (from one RCT: Bracken et al. 1997) that tirilazad mesylate is no more effective than methylprednisolone in promoting neurological recovery in acute SCI individuals.