It is capable of directly potentiating the depolarization of hippocampal CA1 neurons induced through NMDA administration.

Animal studies have shown that nefopam has a potentiating (analgesic-sparing) effect on morphine and other opioids by broadening the antinociceptive action of the opioid and possibly other mechanisms, generally lowering the dose requirements of both when they are used concomitantly.

These drugs alter the neuromodulatory influence of dopamine on the processing of reinforcement signals by prolonging the action of dopamine in the nucleus accumbens or by potentiating the activation of neurons in the VTA and NAC.