Abstract: Quinine is an alkaloid which isolated from the bark of Cinchona sp., native plant from South America, especially in Andes Mountains. Beside the function as an anti-malaria, quinine is used as anti-pyretic, analgesic, treatment for myotonia and nocturnal leg cramps. Nocturnal leg cramps is common clinical problem seen most frequently in the elderly. Quinine therapy was reported to be effective in relieving nocturnal leg cramps. However, due to side effects that appear limited this used. O-desmethyl quinine (C19H22N2O2) is one of quinine active metabolites that lost its methyl group. Therefore, this study was aimed to determine the efficacy and safety O-desmethyl quinine compared to quinine in treatment nocturnal leg cramps. Mice model were established by triction and rota rod method. Rats model were established through spinal cord injury and be evaluated by swimming test for 6 weeks. Test animals of spinal cord injury method were divided into three group consisted of control group, group treated with quinine orally at a dose of 26 mg kg-1 b.wt. and group treated with O-desmethyl quinine orally at a dose 26 mg kg-1 b.wt. On the last day, blood was taken to evaluate hematological profile. O-desmethyl quinine showed reduction frequency of cramps in rats with spinal cord injury. Improvement of quinine group was seen at week 6 and on O-desmethyl quinine group began from week 3 O-desmethyl quinine group showed lower blood toxicity compared to quinine group.