Perphenazine is a depressant which blocks dopamine receptors in the central nervous system. It binds to dopamine D1 and D2 receptors and inhibits their activity. Its antiemetic action is mainly due to the inhibition of D2 receptors in the center of the vomiting. Perphenazine also binds to alpha adrenergic receptors and in conjunction with G proteins activate the phosphatidylinositol-calcium system.
Amitriptyline is a tricyclic antidepressant and an analgesic. It prevents the re-uptake, and hence the inactivation of noradrenaline and serotonin at nerve terminals. Reuptake prevention of these monoamine neurotransmitters potentiate their action in the brain. This appears to be associated with the antidepressant activity.