Because different serotonin receptors they work on and stuff like that. Promethazine is a phenothiazine antihistamine/antipsychotic like Thorazine. Chlorpheniramine is an alkylamine antihistamine. The effects are way different together in the combo as I have tried them each separately, and in all kind of different combos. The best before the quad is... Chlorpheniramine, diphenhydramine, Subutex, Xanax. That is a very good one too. I don't like Diphenhydramine even tho it's the same thing as promethazine pretty much, it's just it's availability and that so many other people do it makes it less interesting to me with my anxiety. When I'm completely xaned out then diphenhydramine would be fine and won't fuck with me even tho I know it's an actual drug like every thing else. Oh my I'm fucked up off this holy Quadruplty combo with gabapentin 300mg thrown it, and is my first time doing gabapentin.