IS METHYLPHENIDATE LIKE COCAINE - STUDIES ON THEIR PHARMACOKINETICS AND DISTRIBUTION IN THE HUMAN BRAIN

Background: The purposes of this study were to investigate the pharmac okinetics of methylphenidate hydrochloride (Ritalin) in the human brai n, to compare them with those of cocaine, and to evaluate whether coca ine and methylphenidate compete for the same binding sites. Methods: W e used positron emission tomography to measure the temporal and spatia l distribution of carbon 11 (C-11)-labeled methylphenidate. These resu lts were compared with those obtained previously for [C-11]cocaine. Ei ght healthy male subjects, 20 to 51 years of age, were scanned with [C -11]methylphenidate. Three were tested twice to assess test-retest var iability, four were tested at baseline and after administration of met hylphenidate, and one was tested with [C-11]methylphenidate and [C-11] cocaine. Two baboons were scanned to evaluate whether there was compet ition between cocaine and methylphenidate for the same binding sites i n the brain. Results: The uptake of [C-11] methylphenidate in the brai n was high (mean+/-SD, 7.5%+/-1.5%), and the maximal concentration occ urred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [C-11]m ethylphenidate was identical to that of [C-11] cocaine and they compet ed with each other for the same binding sites, these two drugs differe d markedly in their pharmacokinetics, Clearance of [C-11]methylphenida te from striatum (90 minutes) was significantly slower than that of [C -11]cocaine (20 minutes). For both drugs, their fast uptake in striatu m paralleled the experience of the ''high.'' For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high parallel ed its fast rate of clearance from the brain. Conclusion: We speculate that because the experience of the high is associated with the fast u ptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in pr omoting its frequent self-administration.