SpringerLink
Log in

Cognitive effects of milacemide and methylphenidate in healthy young adults

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

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 significantdeclines 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albers GW (1990) Potential therapeutic uses ofN-methyl-D-aspartate antagonists in cerebral ischemia. Clin Neuropharmacol 13:177–197

    Google Scholar 

  • Bonhaus DW, Burge BC, McNamara JO (1987) Biochemical evidence that glycine allosterically regulates and NMDA receptor-coupled ion channel. Eur J Pharmacol 142:489–490

    Google Scholar 

  • Bonhaus DW, Perry WB, McNamamara JO (1990) Decreased density, but not number, ofN-methyl-D-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats. Brain Res 532:82–86

    Google Scholar 

  • Buschke H (1973) Selective reminding for analysis of memory and learning. J Verb Learn Behav 12:543–550

    Google Scholar 

  • Buschke H, Fuld PA (1974) Evaluation of storage, retention, and retrieval in disordered memory and learning. Neurology 24:1019–1025

    Google Scholar 

  • Camp JA, Winsberg BG (1984) Clinical utility of animal models of childhood hyperkinesis. Clin Neuropharmacol 7:185–221

    Google Scholar 

  • Christophe J, Kutzner T, Nguyen-Bui ND, Damien C, Chatelain P, Gillet L (1983) Conversion of orally administered 2-n-pentylaminoacetamide into glycinamide and glycine in the rat brain. Life Sci 33:533–541

    Google Scholar 

  • Collingridge GL, Bliss TVP (1987) NMDA receptors — their role in long-term potentiation. Trends Neurosci 10:288–293

    Google Scholar 

  • Collingridge GL, Singer W (1990) Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci 11:290–296

    Google Scholar 

  • Cutler NR, Fakouhi TD, Smith WT, Hendrie HC, Matsuo F, Sramek JJ, Herting RL (1993) Evaluation of multiple doses of milacemide in the treatment of senile dementia of the Alzheimer's type. J Geriatr Psychiatr Neurol 6:115–119

    Google Scholar 

  • Deutsch SI, Mastropaolo J, Schwartz BL, Rosse RB, Morihisa JM (1989) A “glutamatergic hypothesis” of schizophrenia. Clin Neuropharmacol 12:1–13

    Google Scholar 

  • Dixon WJ (ed) (1985) BMDP statistical software manual. 1985 printing. University of California Press, Berkeley

    Google Scholar 

  • Drew CJ (1980) Introduction to designing and conducting research, 2nd edn. Mosby, St Louis

    Google Scholar 

  • Dunn LM, Dunn LM (1981) Peabody Individual Achievement Test-revised. American Guidance Service, Circle Pines, Minn.

    Google Scholar 

  • Dysken MW, Mendels J, LeWitt P, Reisberg B, Pomara N, Wood J, Skare S, Fakouhi JD, Herting RL (1992) Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type. J Am Geriatr Soc 40:503–506

    Google Scholar 

  • Evans RW, Gualtieri CT, Amara I (1986) Methylphenidate and memory: dissociated effects in hyperactive children. Psychopharmacology 90:211–216

    Google Scholar 

  • Gottfries CG (1985) Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. Psychopharmacology 86:245–252

    Google Scholar 

  • Green DM, Swets JA (1966) Signal detection theory and psychophysics. Wiley, New York

    Google Scholar 

  • Greenamyre JT, Young AB (1989) Excitatory amino acids and Alzheimer's disease. Neurobiol Aging 10:593–602

    Google Scholar 

  • Halliday R, Callaway E, Naylor H, Gratzinger P, Prael R (1986) The effects of stimulant drugs on information processing in elderly adults. J Gerontol 41:748–757

    Google Scholar 

  • Handelmann GE, Nevins ME, Mueller LL, Arnolde SM, Cordi AA (1989) Milacemide, a glycine prodrug, enhances performance of learning tasks in normal and amnestic rodents. Pharmacol Biochem Behav 34:823–828

    Google Scholar 

  • Hungund BL, Perel JM, Hurwic MC, Sverd J, Winsberg BG (1979) Pharmacokinetics of methylphenidate in hyperactive children. Br J Pharmacol 8:571–576

    Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531

    Google Scholar 

  • Lawlor BA, Davis KL (1992) Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer's disease? Biol Psychiatry 31:337–350

    Google Scholar 

  • Naylor H, Halliday R, Callaway E (1985) The effect of methylphenidate on information processing. Psychopharmacology 86:90–95

    Google Scholar 

  • Newman RP, Weingartner H, Smallberg SA, Calne DB (1984) Effortful and automatic memory: effects of dopamine. Neurology 34:805–807

    Google Scholar 

  • Paivio A, Yuille JC, Madigan SA (1968) Concreteness, imagery, and meaningfulness values for 925 nouns. J Exp Psychol Monogr Suppl 76 [1/part 2]:1–25

    Google Scholar 

  • Peeke S, Halliday R, Callaway E, Prael R, Reus V (1984) Effects of two doses of methylphenidate on verbal information processing in hyperactive children. J Clin Psychopharmacol 4:82–88

    Google Scholar 

  • Quartermain D (1983) The role of catecholamines in memory processing. In: Deutsch JA (ed) The physiological basis of memory. Academic Press, New York, pp 387–423

    Google Scholar 

  • Quartermain D, Judge ME, Leo P (1988) Attenuation of forgetting by pharmacological stimulation of aminergic neurotransmitter systems. Pharmacol Biochem Behav 30:77–81

    Google Scholar 

  • Quartermain D, Nuygen T, Sheu J, Herting RL (1991) Milacemide enhances memory and alleviates spontaneous forgetting in mice. Pharmacol Biochem Behav 39:31–35

    Google Scholar 

  • Rapoport JL, Buchsbaum MS, Weingartner H, Zahn TP, Ludlow C, Mikkelsen EJ (1980) Dextroamphetamine. Its cognitive and behavioral effects in normal and hyperactive boys and normal men. Arch Gen Psychiatry 37:933–943

    Google Scholar 

  • Saletu B, Gruenberger J (1984) Early clinical pharmacological trials with a new anti-epileptic, milacemide, using pharmaco-EEG and psychometry. Meth Find Exp Clin Pharmacol 6:317–330

    Google Scholar 

  • Saletu B, Gruenberger J, Linzmayer L (1986) Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations. Arch Gerontol Geriatr 5:165–181

    Google Scholar 

  • Schwartz BL, Hashtroudi S, Herting RL, Handerson H, Deutsch SI (1991) Glycine prodrug facilitates memory retrieval in humans. Neurology 41:1341–1343

    Google Scholar 

  • Squire LR (1987) Memory and brain. Oxford University Press, New York, pp 39–55

    Google Scholar 

  • Squire LR, Zola-Morgan S (1991) The medial temporal lobe memory system. Science 253:1380–1386

    Google Scholar 

  • Strauss J, Lewis JL, Klorman R, Peloquin L, Perlmutter RA, Salzman LF (1984) Effects of methylphenidate on young adults' performance and event-related potentials in a vigilance and a paired-associates learning test. Psychophysiology 21:609–621

    Google Scholar 

  • Strupp BJ, Bunsey M, Levitsky D, Kesler M (1991) Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory. Behav Neural Biol 56:62–76

    Google Scholar 

  • Underwood BJ (1983) Attributes of memory. Scott, Foresman, Glenview Ill., pp 210–239

    Google Scholar 

  • Weingartner H, Rapoport JL, Buchsbaum MS, Bunney WE Jr, Ebert MH, Mikkelsen EJ, Caine ED (1980) Cognitive processes in normal and hyperactive children and their response to amphetamine treatment. J Abnorm Psychol 89:25–37

    Google Scholar 

  • Winsberg BG, Camp JA (1981) Psychostimulant therapy for behavior disorders: a status review. In: Ochroch R (ed) The diagnosis and treatment of minimal brain dysfunction in children. A clinical approach. Human Sciences Press, New York, pp 136–146

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nathan S. Kline Institute for Psychiatric Research, 10962, Orangeburg, NY, USA

    Janet A. Camp-Bruno

  2. Searle Research and Development, 4901 Searle Parkway, 60077, Skokie, IL, USA

    Robert L. Herting

Authors
  1. Janet A. Camp-Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert L. Herting
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Camp-Bruno, J.A., Herting, R.L. Cognitive effects of milacemide and methylphenidate in healthy young adults. Psychopharmacology 115, 46–52 (1994). https://doi.org/10.1007/BF02244750

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244750

Key words

Search

Navigation