Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.
The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.
Ghelardini
C
C
Department of Pharmacology, University of Florence, Italy.
Galeotti
N
N
Bartolini
A
A
Furukawa
S
S
Nitta
A
A
Manetti
D
D
Gualtieri
F
F
D000109:Acetylcholine / Q000378:metabolism*; D000647:Amnesia / Q000139:chemically induced / Q000517:prevention & control; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018727:Muscarinic Antagonists / Q000009:adverse effects; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000187:drug effects*; D010666:Phenylpropionates / Q000494:pharmacology*; D012601:Scopolamine / Q000009:adverse effects; D014326:Tropanes / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D018727:Muscarinic Antagonists; D009414:Nerve Growth Factors; D010666:Phenylpropionates; D014326:Tropanes; C087567:N-methyltropan-3-yl 2-(4-bromophenyl)propionate; D012601:Scopolamine; D000109:Acetylcholine