Abstract—Morphine and its nicotinoyl esters, dinicotinoylmorphine (nicomorphine), 6‐mononicotinoylmorphine (6‐MNM) and 3‐mononicotinoylmorphine (3‐MNM) were tested in mice for central activity to obtain time‐effect profiles of these compounds in rats. Two effects, analgesia with the hot plate test and locomotor stimulation in activity cages were measured and nicomorphine, 6‐MNM and 3‐MNM were found to have a faster onset of action compared with morphine. The effects of 3‐MNM and morphine lasted longer than the effect of nicomorphine and 6‐MNM. The prodrug behaviour of 3‐MNM and nicomorphine for morphine and 6‐MNM, res