An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats

Comparison with other cholinesterase inhibitors

Daniela Braida, Emma Paladini, Pierluigi Griffini, Mariapia Lamperti, Antonio Maggi, Mariaelvina Sala

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The potential of heptylphysostigmine tartrate (pyrrolo [2,3b] indol-5-ol, 3,3a,8,8a-hexahydro-1,3a,8-trimethylheptylcarbamate [ester, (3aS-cis)]) (MF201), a new second-generation cholinesterase inhibitor, to antagonize scopolamine-induced amnesia in rats was assessed in an 8-arm radial maze. Upon completing the training session, the rats were orally administered increasing doses of MF201 (2, 3, 4, 6 and 8 mg/kg) 60 min prior to a s.c. injection of scopolamine (0.25 mg/kg). 9-Amino-1,2,3,4-tetrahydroamino- acridine hydrochloride hydrate (tacrine) (0.25, 0.37, 0.5, 1 and 2 mg/kg), 1- benzil-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine (E2020) (0.125, 0.18, 0.25 and 0.5 mg/kg) and physostigmine (0.15, 0.25, 0.5 and 1 mg/kg) were orally administered and rats were tested in the same task. As previously described, scopolamine induced an impairment in radial maze performance, measured in terms of total number of errors, total time taken to complete the task and the percentage of amnesic animals. The reversal of scopolamine- induced impairment was characterized by the presence of an inverted U-shaped dose-response curve. A significant antagonistic effect was achieved with a dose (mg/kg) of 0.25 for E2020, 0.5 for tacrine and physostigmine and 3, 4 and 6 for MF201, the latter manifesting a broader spectrum of activity (3-6 mg/kg). While the maximal active doses restored the scopolamine-induced modified pattern of arm entry, they were ineffective in reducing hypermotility, suggesting the drugs have a specific effect on cognitive function.

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalEuropean Journal of Pharmacology
Volume302
Issue number1-3
DOIs
Publication statusPublished - Apr 29 1996

Fingerprint

Scopolamine Hydrobromide
Cholinesterase Inhibitors
Tacrine
Physostigmine
Amnesia
Cognition
Esters
physostigmine heptyl
Injections
Pharmaceutical Preparations

Keywords

  • (Rat)
  • 8-Arm radial maze
  • E2020
  • MF201
  • Physostigmine
  • Tacrine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats : Comparison with other cholinesterase inhibitors. / Braida, Daniela; Paladini, Emma; Griffini, Pierluigi; Lamperti, Mariapia; Maggi, Antonio; Sala, Mariaelvina.

In: European Journal of Pharmacology, Vol. 302, No. 1-3, 29.04.1996, p. 13-20.

Research output: Contribution to journalArticle

Braida, Daniela ; Paladini, Emma ; Griffini, Pierluigi ; Lamperti, Mariapia ; Maggi, Antonio ; Sala, Mariaelvina. / An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats : Comparison with other cholinesterase inhibitors. In: European Journal of Pharmacology. 1996 ; Vol. 302, No. 1-3. pp. 13-20.
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