Phentermine, like many other prescription drugs, works with neurotransmitters in the brain. It is a centrally-acting stimulant chemically related to the amphetamines. It stimulates neuron bundles to release a particular group of neurotransmitters known as catecholamines; these include dopamine, epinephrine (also known as adrenalin), and norepinephrine (noradrenaline). The anorectic activity seen with these compounds would thus seem likely due to this effect on the central nervous system, which is consistent with current knowledge about central nervous system systems and feeding behavior. This is the same mechanism of action as other stimulant appetite suppressants such as diethylpropion, and phendimetrazine.

The neurotransmitters signal a fight-or-flight response in the body which, in turn, puts a halt to the hunger signal. As a result, it causes a loss in appetite because the brain does not receive the hunger message.