Pyrithioxin (Pyritinol)

Pyritinol reduces nociception and oxidative stress in diabetic rats

The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.

Neurochemical studies on the mechanism of action of pyritinol

In investigations carried out in young and old rats with pyritinol (pyrithioxin, Encephabol), 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Highly sensitive voltamperometric determination of pyritinol using carbon nanofiber/gold nanoparticle composite screen-printed carbon electrode

A novel and highly sensitive electrochemical method for the detection of pyritinol in pharmaceutical products and serum samples has been accomplished based on voltamperometric response of pyritinol in carbon nanofiber-gold nanoparticle (CNF-GNP)-modified screen-printed carbon electrode (SPCE). The electrochemical response of pyritinol to CNF-GNP-modified SPCE was studied by cyclic voltammetry and square-wave voltammetry (SWV). Under optimized working conditions, the novel sensor shows excellent voltamperometric response toward pyritinol. The SWV study shows significantly enhanced electrochemical response for pyritinol in CNF-GNP-modified SPCE providing high sensitivity to the novel sensor for pyritinol detection. The peak current for pyritinol is found to be linear with the concentration in the range 1.0×10^-8-5.0×10^-5 M with a detection limit of 6.23×10^-9 M using SWV as the detection method. The viability of the new developed sensor for the analytical purposes was studied by performing experiments on various commercial pharmaceutical products and blood serum samples, which yielded adequate recoveries of pyritinol. The novel electrochemical sensor provides high sensitivity, enhanced selectivity, good reproducibility and practical applicability.

Pyritinol hydrochloride and cognitive functions: influence on children in slow learner classes

Pyritinol-HCl was tested for its impact on the cognitive functions of children with learning disabilities. This study is a contribution to scientific discussion on the complicated methodologic problems in evaluating the clinical efficacy of psychopharmacologic agents. Sixty-seven pupils of slow learner classes between the ages of 11 and 16 years were treated for 6 months with 300 mg pyritinol-HCl/24 hr or placebo under strict double-blind conditions. Drug intake was stimulated and controlled by means of intense psychosocial interaction with the mothers of the subjects. The dependence variables used to test medication effects were 22 parameters of cognitive performance measured in psychologic tests for perceptual and intellectual functions which were administered immediately before and after the medication phase. First the gainscores before and after treatment with pyritinol or placebo within the 22 cognitive parameters were statistically compared. In addition, an analysis of covariance on the corrected results of the second test (treating the results of first testing as covariates) and a two group discriminant analysis for overall differences were performed. None of the 22 parameters showed statistically significant treatment effects with respect to average performance (t (pyritinol - placebo) = 1.96 to 1.31), neither could the two groups be separated by discriminant analysis (Hotelling's T2 = 35.4, df - 22 and 43, P = 0.465). With respect to a variability of gainscores, however, in four parameters there was a significantly higher variance in the pyritinol group (F = 1.85-2.33, P less than 0.05, less than 0.02, respectively). This fact may signify that pyritinol-HCl had different effects on different subjects. By means of prognostic stratification we therefore attempted to define objective criteria for a selection of subjects with probable positive treatment effects. None of the 15 tested criteria, such as body weight, age, perceptual handicaps, or reduced short term memory, IQ range, proved, however, to be critical for a prognosis of pyritinol effects within the present test population.

On the effects of pyritinol on functional deficits of patients with organic mental disorders

In 120 geriatric patients suffering from cerebral functional disorders with a moderate to rather severe degree of chronic brain syndrome, the effects of pyritinol were investigated in a placebo-controlled, randomized double-blind study. Furthermore, we attempted to find some evidence for the validity of a neurophysiological vigilance model which had already been used earlier. In the previous study it had been possible to show a rise in the vigilance level in patients under pyritinol treatment. The investigation began with a two-week single-blind placebo wash-out phase and continued over a 12-week treatment period, with six weeks' treatment in a hospital ward and six weeks' outpatient treatment (or in a geriatric home within a hospital setting). Pyritinol was administered three times daily in coated tablets each containing 200 mg. The course of the trial was controlled using two rating scales (SCAG, BGP), a physician's Global Impression (GI) and two performance tests (SKT, ZVT-G). There were 13 drop-outs, four because of intercurrent diseases, nine because they did not fulfill the inclusion criteria. The data of 107 patients were included in the statistical analysis, 54 on pyritinol and 53 on placebo. No notable adverse drug reactions were observed that were not similarly reported in the placebo group (Table 1). Statistically significant results were found in favor of pyritinol compared with placebo in both the level of clinical symptomatology (Fig. 1) and the performance level (Fig. 4). Particularly impressive was the superiority of pyritinol in the factor "social behavior" of the SCAG. Considering the clinical relevance of the changes it can be concluded that in both groups improvements occurred.(ABSTRACT TRUNCATED AT 250 WORDS)