ABSTRACT
Acentrally active drug that enhances AMPA receptor-mediated currents was tested for its effects on memory in humans. Evidence for a positive influence on encoding was obtained in four tests: (i) visual associations, (ii) recognition of odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity of playing cards. The drug did not improve scores in a task requiring cued recall of verbal information. The selectivity of drug effects on memory was confirmed using tests of visual recognition, motor performance, and general intellectual functioning. These results suggest that positive modulators of AMPA receptors selectively improve at least some aspects of memory.
Subject(s)
Dioxoles/pharmacology , Memory/drug effects , Piperidines/pharmacology , Receptors, AMPA/drug effects , Receptors, AMPA/physiology , Adult , Association Learning/drug effects , Cues , Humans , Male , Maze Learning , Mental Recall/drug effects , Odorants , Pattern Recognition, Visual/drug effects , Space Perception , Visual PerceptionABSTRACT
Elderly subjects (65-76 years) were tested for recall of nonsense syllables prior to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine (CX516), a centrally active drug that enhances currents mediated by AMPA-type glutamate receptors. A significant and positive drug effect was found for delayed (5 min) recall at 75 min posttreatment; average scores for the highest dose group were more than twofold greater than for the placebo group. The drug had no evident influence on heart rate or self-assessment of several psychological variables.
Subject(s)
Aging/physiology , Dioxoles/administration & dosage , Mental Recall/drug effects , Piperidines/administration & dosage , Receptors, AMPA/agonists , Aged , Blood Pressure , Dioxoles/blood , Heart Rate , Humans , Male , Nootropic Agents/administration & dosage , Nootropic Agents/blood , Piperidines/blood , Psychometrics , Receptors, AMPA/physiology , Time FactorsSubject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/etiology , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Animals , Chromosomes, Human, Pair 14 , Clinical Trials as Topic , Estradiol/therapeutic use , Female , Humans , Male , Mice , Mice, Transgenic , Models, Biological , MutationSubject(s)
Brain/drug effects , Cerebrovascular Disorders/drug therapy , Ischemic Attack, Transient/drug therapy , Plasminogen Activators/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Brain/blood supply , Brain/pathology , Cerebrovascular Circulation/drug effects , Cerebrovascular Disorders/blood , Homeostasis/drug effects , Humans , Ischemic Attack, Transient/blood , Magnetic Resonance Imaging , Male , Microcirculation/metabolism , Middle Aged , Neurons/drug effects , Neurons/metabolism , Plasminogen Activators/administration & dosage , Tissue Plasminogen Activator/administration & dosageABSTRACT
The effects of 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516), a centrally active compound that facilitates AMPA receptor-mediated synaptic responses, were tested in human subjects. Separate tests of delayed recall were given prior to and nearly 3 h after administration of placebo (n = 12) or drug (n = 36). Control subjects exhibited poorer performance in the second session than in the first while subjects given 600-1200 mg of the drug did not. There were no pre- vs post-treatment differences in immediate recall in either group. The drug did not reliably affect self-assessment scores for any of several psychological variables but did disrupt the normally present correlations for within-subject changes in the variables. These results suggest that AMPA receptor modulators may (1) improve memory under some circumstances and (2) produce psychological effects that are subtle or not related to specific mood states.
