Patrick K S, Kilts C D, Breese G R
J Med Chem. 1981 Oct;24(10):1237-40. doi: 10.1021/jm00142a021.
threo-dl-p-Hydroxymethylphenidate and erythro-dl-p-hydroxymethylphenidate (5a and 5b) and the deesterified products, threo-dl- and erythro-dl-p-hydroxyritalinic acid (6a and 6b), were synthesized. The effects of the intracerebroventricular administration of these compounds on the locomotor activity of rats was determined and compared to that of the respective racemates of methylphenidate (1a and 1b) and ritalinic acid (2a and 2b) as a relative index of in vivo dopaminergic activity. The maximal locomotor response was significantly greater for 5a than for 5b, 1a, or 1b. These findings suggest that metabolite 5a may play a role in the pharmacology of 1a. The intracerebroventricular administration of acids 2a, 2b, 6a, and 6b all produced a small increase in locomotor activity relative to their methyl esters which was not appreciably affected by stereochemistry or para-hydroxylation.
合成了苏式-dl-p-羟甲基哌醋甲酯和赤式-dl-p-羟甲基哌醋甲酯（5a和5b）以及脱酯产物苏式-dl-和赤式-dl-p-羟基利他林酸（6a和6b）。测定了这些化合物脑室内给药对大鼠运动活性的影响，并将其与哌醋甲酯（1a和1b）和利他林酸（2a和2b）各自的外消旋体进行比较，作为体内多巴胺能活性的相对指标。5a的最大运动反应显著大于5b、1a或lb。这些发现表明代谢物5a可能在1a的药理学中起作用。相对于它们的甲酯，脑室内给予酸2a、2b、6a和6b均使运动活性略有增加，这不受立体化学或对羟基化的明显影响。
