I donâ€t relay on Benadryl (diphenhydramine) in that situation as it is unreliable. No matter what help you seek you need to try it at home or on a car ride first to determine how a given product affects (or doesnâ€t affect) your pupppy. The standard diphenhydramine dose is 1mg/pound. There are several â€œnaturalâ€ calming agents some of which work on one pup and not another so they should be tried first also. Zylkene is one example that I have used with some success. Probably the product that most veterinarians turn to is acepromazine which is a prescription tranquilizer, is has the advantage of predictability. It also should be tried before the actual trip to determine optimum dose for your puppy.