The only over-the-counter cat sedative that most veterinarians recommend is Diphenhydramine, as stated on CatChannel and PetMD. This antihistamine is not a true sedative, but can have a calming effect on some animals by making them drowsy.
When dealing with an anxious cat or wanting to keep the cat calm during travel, owners can use a sedative to help kitty relax. Not all owners want to pay for a prescription sedative for the occasional episode. If the cat is healthy and has been checked by the veterinarian, owners may consider using an antihistamine. A very common medication, Diphenhydramine, is sometimes useful for keeping pets calm. Also known under the brand name Benadryl, this medication is sometimes prescribed by veterinarians to help prevent scratching from skin irritation and allergies. Pets, especially those on mood-altering or anti-seizure medication, will feel sleepy after taking Diphenhydramine.
Because cats are much smaller than humans, the recommended dosage is smaller. Pet owners can give about 1 milligram of the antihistamine per pound of cat's weight every 8 hours. For instance, a cat weighing 15 pounds requires a 15 milligram dose of Benadryl. Human dosages are larger, so it may be necessary to cut the pill to get the right amount.