Low doses of risperidone and morphine interact to produce more analgesia and greater extrapyramidal effects in rats.

The search for non-narcotic drugs that will enhance the analgesic effects of opiates without enhancing their side effects has included the investigation of psychoactive drugs already approved for other uses. Some research has supported an analgesic effect of risperidone (RIS), an atypical neuroleptic. However, the analysis of the analgesic efficacy of RIS alone or as an adjuvant to morphine (MOR) has not considered the production of adverse motor effects that would limit its usefulness as a treatment for pain. We tested whether low doses of RIS would enhance the analgesic action of opiates without inducing untoward motor effects. The analgesia induced by a range of RIS doses (0.1-1.0 mg/kg, SC) was assessed alone and in combination with MOR (5 mg/kg, IP) in male Long-Evans (hooded) rats using two different algesiometric assays: hotplate and tail-flick test. The presence or absence of ptosis, vacuous chewing, and abnormal stationary postures was recorded to evaluate dyskinetic effects. No dose of RIS alone altered pain threshold. However, the highest dose of RIS, 1.0 mg/kg SC, significantly increased the analgesic effects of MOR. Dyskinetic effects of RIS were dose-dependent and enhanced in RIS+MOR treatment. These results do not support the hypothesis that RIS, alone or in combination with MOR, elevates pain threshold without also inducing motor side effects. These findings suggest caution in the use of RIS as either a primary treatment or opiate adjuvant treatment for pain.