Neurochemical studies on the
mechanism of action of Pyritinol
Greiner HE, Haase AF, Seyfried CA.
Department of Neurochemistry,
E. Merck, Darmstadt, FRG.
Pharmacopsychiatry 1988 Aug;21pharmacology:26-32
Biological Research, Department of
Neurochemistry, E. Merck, Darmstadt, FRG.
In investigations carried out in young and old rats with pyritinol (pyrithioxin), a substance that is frequently applied in cognitive function
disturbances, besides effects on general cerebral functions, possible
interactions with cholinergic transmission were determined.
The following results were obtained:
1. The adenosine triphosphate (ATP) content of the blood was determined as a
possible biochemical parameter of erythrocyte flexibility. After acute
oral administration of 30, 100, and 300 mg/kg pyritinol, the ATP content of
whole blood increased by 8%, 17% and 20% respectively compared with
2. According to the literature, brain glucose
utilisation is considerably reduced at higher age. This was confirmed in
old rats in the investigation presented here. Pyritinol (200 mg/kg p.o.)
induced a significant increase in glucose utilisation in striatum, cortex,
hypothalamus and cerebellum in 24- to 36-month-old rats.
3. The high-affinity choline uptake in striatal
synaptosomes of old rats was significantly lower than that of young
ones. Pyritinol (600 mg/kg p.o.) increased choline uptake in young rats
as well as in old ones.
4. cGMP can serve as a postsynaptic marker for
the activity of the cholinergic system. Pyritinol (200, 600, 1000 mg/kg
p.o., 16-23 days) increased the cGMP level in the cortex by 25%, 42% and 71%
respectively. Our results are in accordance with the recently described
(Martin, 1987) elevation of cortical acetylcholine levels and facilitation of
acetylcholine release under pyritinol and extend the functional relevance of
these findings to the postsynaptic, cholinergically innervated cortical