Effects of tramadol and its enantiomers on Concanavalin-A induced-proliferation and NK activity of mouse splenocytes: involvement of serotonin

The centrally acting analgesic drug tramadol is a 1:1 racemic mixture of tw o enantiomers, with different pharmacological properties. The (-)-tramadol preferentially inhibits noradrenaline uptake, whereas the (+)-tramadol inhi bits serotonin uptake and binds to opioid receptors. Since tramadol has bee n shown to stimulate some immune responses in mice, in the present work we analyzed the effects of its enantiomers on the same parameters, with the ai m to better characterize the mechanisms involved in such action of tramadol . The acute administration of 20 and 40 mg/kg of racemic tramadol and of 10 and 20 me/kg of (+)-tramadol induced a significant and comparable stimulat ion of Concanavalin-A (Con-A) induced proliferation and of Natural Killer ( NK) activity of splenocytes. On the contrary, the (-)-tramadol was devoid o f any effect. The pretreatment with the serotoninergic antagonist metergoli ne (3.0 mg/kg) completely blocked the effects of both tramadol and (+)-tram adol. We suggest that the enhancement of the serotoninergic tone could be a t the basis of the stimulatory effects exerted by tramadol on Con-A induced lymphoproliferation and NK activity. (C) 1999 International Society for Im munopharmacology. Published by Elsevier Science Ltd. All rights reserved.