This posting is older than 6 months and can contain outdated information.
Thanks for asking.
What you'd need to do:
1) Go to Prefs > Hardware > Built-In IR Receiver
2) Enable support for multiple remotes
3) Create a second "logical remote" by clicking on "+" below the table on the left
4) Press a button on each remote, so you can see two entries in the right table.
5) In the right table, assign a different "logical remote" to each of your two remotes listed on the right
If you want to use each remote solely with Plex and iTunes respectively:
1) Go to Prefs > Mapping > Global mapping
2) Select the respective iTunes and Plex actions that you want to have "hard-wired" to your remote's buttons for the respective remote
Best regards,
Felix Schwarz