Cognitive effects of milacemide and methylphenidate in healthy young adults

Abstract

Cognitive effects of the novel glycine prodrug milacemide (400 mg), the catecholaminergic agonist methylphenidate (20 mg), and placebo were evaluated in 48 healthy young adults. Throughout a 6-h drug treatment day, subjects repeatedly performed tests of target-detection vigilance, immediate and delayed verbal free recall, and Buschke Selective Reminding; total free recall and forced-choice recognition tests were administered at the end of the day. Significant improvement in both vigilance reaction time and Selective Reminding Sum Recall was observed in the methylphenidate group. Contrary to expectations, the milacemide group evidenced significant declines in both vigilance perceptual sensitivity and free-recall difference scores (delayed-immediate). Vigilance reaction times significantly decreased over repeat testing in all groups, but only the methylphenidate group differed from placebo. The reaction-time functions for milacemide and placebo were similar, suggesting arousal was not diminished under milacemide and could not account for the cognitive decrements. No significant drug effects obtained for total free recall or recognition performance. Although the glycine prodrug milacemide was ineffective as a cognitive enhancer, the involvement of the NMDA receptor in memory function reported in the literature supports continued exploration of other approaches for manipulating NMDA receptor activity.

Effects of methylphenidate on working memory in pigeons

“…However, the evidence offered by most of the studies reporting improvements is not convincing. It has been reported that within studies, MPH had an effect on one sample (Galynker et al, 1997;Prendergast et al, 1998), one type of working memory task (Aman et al, 1991;Camp-Bruno & Herting, 1994), or one type of error (Mehta et al, 2000), but not on another. Camp-Bruno and Herting's report that MPH improved the learning of words, as compared with a placebo, was based on results that were significant at p , .10, which is usually considered not statistically significant.…”

“…It is possible that the apparent inconsistencybetween the present results and those in studies that have found that MPH improved memory in humans (Aman et al, 1991;Camp-Bruno & Herting, 1994;Galynker et al, 1997;Mehta et al, 2000;Rapport et al, 1993) is due to species differences between samples. However, the dopaminergic systems of pigeons and mammals are highly similar (Karle, Anderson, Medina, & Reiner, 1996), and the neostriatum caudolaterale of pigeons is believed to be equivalent to the mammalian prefrontal cortex (Hartmann & Gunturkun, 1998), an area that is involved in memory, attention, and the effects of MPH (Mehta et al, 2000;Puumala & Sirvio, 1998;Ragozzino, 2000).…”

“…Mehta et al (2000) found that, administered to healthy adult males, MPH (40 mg) significantly reduced search errors of one type, but not of another, in a spatial working memory task. Similarly, 20 mg MPH improved healthy young adults' learning of lists of difficult words presented aurally but did not improve free recall of easy words presented visually (Camp-Bruno & Herting, 1994). Aman et al (1991) found that MPH (0.4 mg/kg/day) improved the accuracy of children with subaverage IQs on a delayed matchingto-sample task but did not affect their performance in another working memory task, which required them to indicate whether a picture was a member of an earlier presented array.…”

Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review

“…Contrary to a preliminary encouraging study [89], milacemide (400 mg, single dose) did not improve cognitive performance in healthy adults, and was even associated with decreases in some vigilance performances [90]. The research on this substance was discontinued afterwards.…”

Single Dose Methylphenidate Does Not Impact on Attention and Decision Making in Healthy Medical Students

“…In spite of the widespread use of MPH as a cognitive enhancer, multiple cognitive tasks have not unequivocally demonstrated its efficacy in healthy adults. For example, although MPH enhanced vigilance in two studies [6,7], other research found this effect only under special conditions such as task novelty [8] or its challenging nature [9]. Conflicting data was found for the effect of MPH under conditions of sleep deprivation, enhancing vigilance in nine sleep deprived individuals [10] but ineffective in 20 other carefully selected students whether sleep deprived or not [11].…”