Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268)

Daniela Braida, Emma Paladini, Pierluigi Griffini, Mariapia Lamperti, Luisa Colibretti, Mariaelvina Sala

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In the present study a short (120 min) and long-lasting (360 min) antagonism of scopolamine-induced amnesia in rats was investigated in an eight-arm radial maze, by (3a, S. 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8- trimethylpyrrolo[2,3-b]indol-5-ol[8-(cis2,6,-dimethyl-morpholin-4-yl)octyl]- carbamate hydrate (MF268), a new cholinesterase inhibitor. Upon completing the training session, the rats were orally administered increasing doses of ME268 (2, 3, 6, 7, and 8 mg/kg) 60 min prior to SC injection of scopolamine (0.25 mg/kg). Following a further 60 min the rat was placed in the maze. The reversal of scopolamine induced impairment was characterized by an inverted U-shaped dose response curve. A significant reduction in the number of errors, and time taken to complete the maze was observed with a dose of 6 mg/kg. The compound improved memory retention without affecting scopolamine- induced hypermotility. When the same dose was administered 360 min prior to the test a significant reduction in the number of amnesic animals was observed, whereas no cognitive improvement was detected when either 1-Benzil 4 [(5,6 dimethoxy-1-indanon) 2 yl]-methyl piperidine hydrochloride (E2020) (0.2 mg/kg) or tacrine (0.5 mg/kg) were administered 360 min prior to the test. The kinetics of whole-brain cholinesterase confirmed the long-lasting activity for MF268. A clinical relevance for the use of MF268 in AD treatment is suggested.

Original languageEnglish
Pages (from-to)897-901
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume59
Issue number4
DOIs
Publication statusPublished - Apr 1998

Fingerprint

Scopolamine Hydrobromide
Cholinesterase Inhibitors
Rats
Tacrine
Amnesia
Carbamates
Cholinesterases
Hydrates
Brain
Animals
Data storage equipment
Injections
Kinetics
Therapeutics

Keywords

  • Brain cholinesterase
  • E2020
  • Inhibition
  • Locomotor activity
  • MF268
  • Radial maze
  • Rat
  • Tacrine

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Braida, D., Paladini, E., Griffini, P., Lamperti, M., Colibretti, L., & Sala, M. (1998). Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268). Pharmacology, Biochemistry and Behavior, 59(4), 897-901. https://doi.org/10.1016/S0091-3057(97)00526-1

Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268). / Braida, Daniela; Paladini, Emma; Griffini, Pierluigi; Lamperti, Mariapia; Colibretti, Luisa; Sala, Mariaelvina.

In: Pharmacology, Biochemistry and Behavior, Vol. 59, No. 4, 04.1998, p. 897-901.

Research output: Contribution to journalArticle

Braida, D, Paladini, E, Griffini, P, Lamperti, M, Colibretti, L & Sala, M 1998, 'Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268)', Pharmacology, Biochemistry and Behavior, vol. 59, no. 4, pp. 897-901. https://doi.org/10.1016/S0091-3057(97)00526-1
Braida, Daniela ; Paladini, Emma ; Griffini, Pierluigi ; Lamperti, Mariapia ; Colibretti, Luisa ; Sala, Mariaelvina. / Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268). In: Pharmacology, Biochemistry and Behavior. 1998 ; Vol. 59, No. 4. pp. 897-901.
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