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Propofol Hemisuccinate Suppresses Cortical Spreading Depression
Neuroscience Letters (2012)
  • Ashish Dhir, University of California - Davis
  • Christoph Lossin, University of California - Davis
  • Michael A. Rogawski, University of California - Davis
Abstract
Propofol is a rapidly acting water-insoluble non-barbiturate anesthetic agent that is widely used as an intravenous sedative-hypnotic agent. Anecdotal evidence indicates that propofol may be effective at terminating intractable migraine headache. Cortical spreading depression (CSD) is believed to be the neural correlate of migraine aura and may be a trigger for migraine pain. Agents that block the induction or slow the spread of CSD may be of utility in treating migraine. Here we examined the ability of propofol hemisuccinate (PHS), a water-soluble prodrug of propofol, to affect CSD in mice. For comparison, we examinined dizocilpine, an NMDA receptor antagonist, that is well recognized to inhibit CSD. When administered 15 min prior to activation of CSD by KCl application to the cortex, intraperitoneal PHS at doses of 120 and 200 mg/kg decreased the number of CSD deflections without an effect on CSD amplitude, and at 200 mg/kg caused a 77% reduction in CSD velocity. The minimally-effective dose of PHS (120 mg/kg) did not cause sedation or motor impairment and while some animals receiving 200 mg/kg did demonstrate motor impariment none exhibited loss-of-righting reflex (anesthesia). Dizocilpine produced comparable inhibition of CSD at doses of 0.5 and 2.5 mg/kg. We conclude that acute PHS treatment inhibits CSD. Our results indicate that propofol, or its prodrug PHS, are worthy of further investigation as a treatment for migraine.
Publication Date
February 25, 2012
Publisher Statement
Available at: http://dx.doi.org/10.1016/j.neulet.2012.02.058
Citation Information
Ashish Dhir, Christoph Lossin and Michael A. Rogawski. "Propofol Hemisuccinate Suppresses Cortical Spreading Depression" Neuroscience Letters Vol. 514 (2012)
Available at: http://works.bepress.com/michael_rogawski/45/