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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 67-70 |
| Number of pages | 4 |
| Journal | Neuroscience Letters |
| Volume | 514 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 11 2012 |
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Keywords
- Cortical spreading depression
- Dizocilpine
- Migraine
- Propofol hemisuccinate
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Propofol hemisuccinate suppresses cortical spreading depression. / Dhir, Ashish; Lossin, Christoph; Rogawski, Michael A.
In: Neuroscience Letters, Vol. 514, No. 1, 11.04.2012, p. 67-70.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Propofol hemisuccinate suppresses cortical spreading depression
AU - Dhir, Ashish
AU - Lossin, Christoph
AU - Rogawski, Michael A
PY - 2012/4/11
Y1 - 2012/4/11
N2 - 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.
AB - 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.
KW - Cortical spreading depression
KW - Dizocilpine
KW - Migraine
KW - Propofol hemisuccinate
UR - http://www.scopus.com/inward/record.url?scp=84859001837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859001837&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2012.02.058
DO - 10.1016/j.neulet.2012.02.058
M3 - Article
VL - 514
SP - 67
EP - 70
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -