Research articleS-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats

- S-adenosyl methionine (SAM) reversed tolerance to morphine analgesia in tail flick test in rats.
- Repeated SAM per se dosing showed analgesic activity which was reversed by naloxone.
- Combining SAM with sub therapeutic dose of morphine also attenuated SAM analgesia.

BackgroundDevelopment of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance.MethodsMale 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7 mg/kg), intraperitoneally (i.p.), once daily for 5 days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800 mg/kg was administered orally (p.o.), 45 min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated.ResultsCo-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration.ConclusionSince safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated.