Hylands Calms Forte -- 2 tablets work on a 400 pound human or a 5 pound dog. It's a homeopathic so it's not going to make him groggy at all. It will 'urge' him to sleep but he'll wake up when you need him to. (health store item)
Ok -- as a HUMAN I get car sick. The **Worst** thing I can do is look out a *side* window. Will make me rolf every time. The trigger is usually pretty individual -- but either have him ABLE to look out a window or maybe **not** able to look out. Luna does FAR better in my PT cruizer than she did in my Contour -- because she doesn't "look out" ....
to desensitize this you need to do it in TINY increments. Get in and out of the car only. Then just ride 10' to the mail box. then back out of the driveway and back in ...
No food before. GIVE something calming (either the Calms Forte or even something like valerian root tincture (works in about 5 minutes -- and 2 droppersful would be fine for a mastiff). The valerian is a relaxant not a sedative.
But trail it out over weeks t0 desensitize. It will take you a week to even get around a block. Keep it very short. notice what trips his trigger -- stop and go is bad? Does he get wigged at lights? or is he fine until you swerve or switch lanes.