05). Friedman et al compared diphenhydramine 25 mg IV plus trimethobenzamide 200 mg IM to sumatriptan 6 mg SQ.13 The study originally was designed only to demonstrate that the combination of trimethobenzamide and diphenhydramine was superior to sumatriptan, which the investigators failed to demonstrate.

Pain reduction (11-PPS) at 2 hours was similar (trimethobenzamide/diphenhydramine −4.4 vs sumatriptan −6.1). Kostic et al compared diphenhydramine 12.5 mg IV plus prochlorperazine 10 mg IV to sumatriptan 6 mg SQ.14 Pain reduction (VAS) was significantly greater for the diphenhydramine/prochlorperazine group (−73 vs −50; P < .05). Nine of 31 patients in the prochlorperazine/diphenhydramine group reported restlessness, but none needed treatment. Lane et al found that Seliciclib in vitro the combination of dimenhydrinate 25 mg IV plus meperidine 0.4 mg/kg IV was not as effective as chlorpromazine 0.1 mg/kg IV (up to 3 doses).17 Stiell et al found no advantage of dimenhydrinate 50 mg IV plus meperidine 75 mg IM over methotrimeprazine 37.5 mg IM.23 Tek and Mellon compared hydroxyzine 50 mg IM, nalbuphine 10 mg IM, a combination of hydroxyzine and nalbuphine IM, and placebo/NS IM; for patients without aura, headache relief at 1 hour was greatest in the nalbuphine alone group compared with the other groups (nalbuphine −2.16 vs nalbuphine/hydroxyzine −1.42 vs hydroxyzine −1.00 vs placebo −0.89; P < .01).46 Belgrade et al compared

hydroxyzine 50 mg IM plus meperidine 75 mg IM to DHE 1 mg IV plus metoclopramide 10 mg IV and to butorphanol BMS-354825 cost 2 mg IM; pain reduction

(VAS) was significantly greater with DHE/metoclopramide (−59) and butorphanol (−54) vs meperidine/hydroxyzine (−37; P < .01).41 Duarte et al found pain reduction (VAS) with hydroxyzine 50 mg IM plus meperidine 100 mg IM was similar to ketorolac 60 mg IM (−33.7 vs −33.5; P = .76); nausea and drowsiness were not more frequent with hydroxyzine/meperidine (48% vs 28%; P = .15).47 Klapper and Stanton compared hydroxyzine 75 mg IV plus meperidine 75 mg IM to DHE 1 mg IV plus metoclopramide 10 mg IV; pain reduction (4-PPS) was greater with DHE/metoclopramide (−2.14 vs −0.86; P = .006).42 Granisetron, a 5-HT3 antagonist, is useful as an anti-emetic in the treatment of migraine. Other 5-HT3 receptor antagonists have been shown to reduce PRKD3 inflammatory pain in rats.48 Rowat et al compared granisetron 40 and 80 µg IV to placebo/NS IV.49 Neither dose of granisetron produced greater pain reduction (VAS) at 2 hours compared with placebo (40 µg −15 vs 80 µg −13 vs placebo −10). Side effects included gastrointestinal GI symptoms, dizziness, and altered taste. Table 4 summarizes the studies involving the antihistamines and 5HT3 antagonists. Valproate increases γ-aminobutyric acid (GABA) levels in the brain, reduces serotonergic cell activity in the dorsal raphe nucleus, and reduces central activation in the trigeminal nucleus caudalis.