Ganta and Fee noted that it could reduce the incidence of pain caused by propofol injections. They found that 5 mg of metoclopramide and lidocaine administered immediately before propofol was introduced into the dorsal hand vein was equally effective in reducing pain from propofol injections compared to 10 mg of lidocaine and saline (metoclopramide: 23.5%, lidocaine: 21.1%, control: 49.4%). Mecklem[56] compared the effect of 20 mg metoclopramide mixed with 200 mg propofol and 10 mg lidocaine mixed with 200 mg propofol on the prevention of pain after propofol injection. He found that the rates of injection pain were similar in both groups, with a lower rate of nausea in the metoclopramide group.

Trinitroglycerin Wilkinson et al. showed that a 5 mg trinitroglycerin patch placed on the back of the hand 20 minutes before propofol injection significantly reduced the incidence and severity of pain from propofol injection from 67% to 33%. There were no reports of headache or postural hypotension. They hypothesized that vein size, vasospasm, and blood flow were important factors in determining pain associated with propofol injections. Trinitrate causes venous dilation, increases venous flow, diluts the drug, and reduces contact between propofol and the blood vessel wall.

Thiopentanone Lee et al. in a study comparing the effects of pre-administration of 100 mg thiopentanone, 20 mg lidocaine, and saline before propofol injection, found that thiopentanone was significantly more effective than docaine in reducing pain from propofol injection (control group: 50%, thiopentene: 12%, lidocaine: 28%). The mechanism is unclear, but they believe it may be a central or peripheral role. Its central effect may be the synergistic effect between subhypnotic doses of thiopental and propofol. Its peripheral action may be a local mechanism affecting kinin release, pH changes, or the effect of thiopentanone on the lipid solubility and free water concentration of propofol.