A 1-heteroaryl-4-piperidinyl-methyl pyrrolidinone, BMY 21502, delays the decay of hippocampal synaptic potentiation in vitro.
The effects of the substituted pyrrolidinone, BMY 21502, on the properties of cell membranes, synaptic transmission and synaptic plasticity, were assessed in area CA1 of hippocampal slices from the rat. Application of the compound to the bath had no consistent direct effects on parameters of the cell membrane or evoked synaptic potentials, at concentrations of less than 30 microM. In a blind experimental design, BMY 21502 at 1.0 and 10 microM, but not 25 microM, significantly delayed the decay of long-term potentiation in slices obtained from young animals; in slices obtained from very old rats (2.5-3.2 yr), 10 microM BMY 21502 significantly delayed decay of long-term potentiation. Therefore BMY 21502 was active in a physiological model that may predict of cognitive enhancement.
Gribkoff
V K
VK
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Bauman
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LA
VanderMaelen
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CP
D000375:Aging; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011619:Psychotropic Drugs; D011743:Pyrimidines; D011760:Pyrrolidinones; C064122:BMY 21502