Effects of subchronic
administration of pyritinol on receptor deficits and phosphatidylinositol
metabolism in the brain of the aged mouse.
Hartmann H, Cohen SA, Muller WE.
Department of Psychopharmacology,
Central Institute of Mental Health,
Neuropharmacology 1993 Feb;32(2):119-125
The effect of pyritinol, a commonly used nootropic drug,
on receptor properties and function was investigated in different neuronal
systems, possibly associated with age-related decline in brain function.
Chronic treatment (15 days) of aged (22 months) female NMRI mice with
pyritinol (200 mg/kg) restored the reduced density of N-methyl-D-aspartate
receptors in the aged mouse brain. Furthermore, the total number of
binding sites of the alpha 2-receptor ([3H]yohimbine binding) decreased after
treatment with drug, while the number of high-affinity agonist binding sites
([3H]UK 14304 binding) was not changed. In both systems, receptor
affinity was not influenced. The densities of other receptors
investigated (muscarinic-cholinergic, benzodiazepine and beta-adrenergic) were
not altered by treatment with pyritinol. Additionally, the effect of
pyritinol on phosphatidylinositol (PI) metabolism was investigated in
dissociated neurones from young and aged mice. Muscarinic-cholinergic induced
accumulation of phosphatidylinositol and the inositol phosphate response due
to activation of G-protein by fluoride was increased in aged animals, treated
with drug. The inositolphosphate response after stimulation with
pilocarpine was slightly but not significantly increased. The metabolism of
phosphatidylinositol in young animals was not altered by treatment with
drug. These results support the hypothesis of a nootropic-mediated
restoration of age-related brain deficits. Changes caused by pyritinol
may be due to beneficial effects on age-related alterations of the properties
of the neuronal membrane.