Interaction between bromocriptine and levodopa. Biochemical basis for an improved treatment for parkinsonism

The present investigation examined the biochemical interaction of bromocriptine and levodopa with respect to monoamine and gamma-aminobutyric acid metabolism in the brain. Rats were treated with levodopa, 250 mg per kilogram of body weight intraperitoneally, with or without carbidopa, 25 mg per kilogram, 1 or 2 hours before sacrifice. Some were also given bromocriptine, 5.0 mg per kilogram, 4 hours before sacrifice. Rats were killed 1 and 2 hours after levodopa and brain levels of gamma-aminobutyric acid and monoamines, and their metabolites were measured. Dopamine levels and metabolism were not markedly altered when bromocriptine was added to levodopa treatment. The level of serotonin, which was reduced 25 to 40 percent by levodopa alone, was close to normal with the combination treatment. Serotonin metabolism was also enhanced by the addition of bromocriptine as shown by increased levels of 5-hydroxyindoleacetic acid. The results suggest that bromocriptine not only may improve the motor disorder of parkinsonism but also may reduce some side effects of levodopa therapy, such as depression, which could be due to serotonin depletion.