Doig's second-half header ensured that Northampton won
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Leyton Orient suffered an FA Cup hangover as they slumped to a sixth home defeat of the season.
Scott McGleish opened the scoring for the visitors against his former club, as he pounced when keeper Glyn Garner failed to hold a shot from Jason Lee.
Garner was later forced off after colliding with Lee and substitute Glenn Morris stood no chance with Chris Doig's header from David Hunt's corner.
Daryl McMahon netted for Orient on 85 minutes, but it was not enough.
Leyton Orient: Garner (Morris 50), Miller (Carlisle 77), Mackie, Zakuani, Lockwood, Tudor, Simpson, McMahon, Keith (Steele 67), Alexander, Ibehre.
Subs Not Used: Barnard, Demetriou.
Booked: McMahon.
Goals: McMahon 86.
Northampton: Harper, Chambers, Doig, Dyche, Low (Bojic 71), Hunt, Taylor, Lee, Crowe, Kirk (Jess 78), McGleish.
Subs Not Used: Bunn, Smith, Mendes.
Booked: Lee.
Goals: McGleish 35, Doig 54.
Att: 5,445
Ref: R Booth (Nottinghamshire).