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Journal of Pharmacology and Experimental Therapeutics

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OtherBEHAVIORAL PHARMACOLOGY

FK960 [N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide Monohydrate], a Novel Potential Antidementia Drug, Improves Visual Recognition Memory in Rhesus Monkeys: Comparison with Physostigmine

Nobuya Matsuoka and Thomas G. Aigner
Journal of Pharmacology and Experimental Therapeutics March 1997, 280 (3) 1201-1209;
Nobuya Matsuoka
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Thomas G. Aigner
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Abstract

Our previous studies demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various rodent models of amnesia, through activation of the somatostatin neuronal system. To extend the antiamnesic action of FK960 to nonhuman primates, FK960 was evaluated for its ability to reverse the deficits in visual recognition memory produced by muscarinic cholinergic receptor blockade by scopolamine or N-methyl-d-aspartate receptor blockade by dizocilpine (MK-801) in four rhesus monkeys performing a computer-automated version of delayed nonmatching to sample, with a list length of 20 trial-unique graphic symbols. Furthermore, the effects of FK960 were compared with those of physostigmine, a cholinesterase inhibitor. Doses of FK960 (1, 3.2, 10, 32, 100, 320 or 1000 μg/kg) injected i.m. 30 min before testing minimally affected visual recognition memory when administered alone. FK960 (1, 3.2, 10 or 32 μg/kg) significantly antagonized the deficits in visual recognition memory produced by scopolamine (10 μg/kg); the same doses of the drug minimally affected the deficits produced by dizocilpine (32 μg/kg). Similarly, physostigmine (3.2, 10 or 32 μg/kg) significantly and dose-dependently restored the visual recognition memory deficits produced by scopolamine (10 μg/kg) but not those produced by dizocilpine (32 μg/kg). From these results, we conclude that FK960 improves deficits in recognition memory associated with central cholinergic hypofunction in nonhuman primates, and we suggest that the therapeutic potential of this drug for patients with dementia should be evaluated.

Footnotes

  • Send reprint requests to: Thomas G. Aigner, Ph.D., National Institute on Drug Abuse, Parklawn Bldg., Room 10A-19, 5600 Fishers Lane, Rockville, MD 20857.

  • ↵1 Present address: National Institute on Drug Abuse, Parklawn Bldg., Room 10A-19, 5600 Fishers Lane, Rockville, MD 20857.

  • Abbreviations:
    AD
    Alzheimer’s disease
    ANOVA
    analysis of variance
    DNMS
    delayed nonmatching-to-sample
    LTP
    long-term potentiation
    NMDA
    N-methyl-d-aspartate
    • Received April 8, 1996.
    • Accepted November 27, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 3
1 Mar 1997
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OtherBEHAVIORAL PHARMACOLOGY

FK960 [N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide Monohydrate], a Novel Potential Antidementia Drug, Improves Visual Recognition Memory in Rhesus Monkeys: Comparison with Physostigmine

Nobuya Matsuoka and Thomas G. Aigner
Journal of Pharmacology and Experimental Therapeutics March 1, 1997, 280 (3) 1201-1209;

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OtherBEHAVIORAL PHARMACOLOGY

FK960 [N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide Monohydrate], a Novel Potential Antidementia Drug, Improves Visual Recognition Memory in Rhesus Monkeys: Comparison with Physostigmine

Nobuya Matsuoka and Thomas G. Aigner
Journal of Pharmacology and Experimental Therapeutics March 1, 1997, 280 (3) 1201-1209;
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