Keep him in the carrier in the vehicle, you're right it's safer, and it's also less stressfull.
I used to have a client who transported her cats in the car in pillowcases. No kidding. She decided once to get them all carriers, and the cats were misrable, howled and clawed and peed in the carriers.. horrible. She went back to bagging them. But this was only from house to our shop.. not long distance.
With a large carrier, you could offer a small litter pan, but I'll bet he'll want to hold it until he's not moving. It'll be there should he want to use it, but offer him a litter pan when you stop for the night. The main thing I'd worry over is the vehicle getting hot if you get out to get food, potty, etc. As long as you don't leave him alone, you should be fine.
Try catnip before you try the drugs. Some cats on the drugs act really horrible and wild, they start tripping and see things, and panic. Catnip normally is a lot easier on them.
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