Neurochemical studies on the mechanism of action of Pyritinol

Greiner HE, Haase AF, Seyfried CA.

Biological Research, 
Department of Neurochemistry, 
E. Merck, Darmstadt, FRG.
Pharmacopsychiatry 1988 Aug;21pharmacology:26-32

ABSTRACT

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 placebo. 

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 neurons.

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