[Pyrithioxine (Encephabol); report of a double blind study of the action of pyrithioxine (Encephabol) in patients suffering from central deafness].
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Effects of single doses and daily administration of pyrithioxine (pyritinolum,NFN, RINN) on the alcohol withdrawal syndrome in rats.
Male Wistar rats were made physically dependent on ethanol by intragastric administration (4-10 g/kg/day) for 20 days. The dose of ethanol was adjusted to maintain the maximal level of intoxication compatible with adequate intake of a liquid diet. After withdrawal of ethanol a few animals developed spontaneous tonic-clonic convulsions. A marked increase in susceptibility to sound-induced convulsions and decrease in sensitivity to pain were observed in the rats after withdrawal, and their serum and red cell Mg++ contents were found to be significantly lower and red cell K+ content higher than in controls. Therapeutic amounts (0.01 g/kg/day) of pyrithioxine (pyritinolum NFN, rINN) (bis-3-hydroxy-4-hydroxymethyl-2-methylpyridyl-(5)-methyl)-disulphide dihydrochloride monohydrate) given with the ethanol for 20 days made the rats with withdrawal symptoms significantly more responsive to pain and slightly but insignificantly less susceptible to sound-induced withdrawal convulsions, but this pretreatment did not markedly prevent the deviations in electrolyte concentrations. Large amounts of the drug (0.2-0.3 g/kg/day), however, increased the number of spontaneous withdrawal convulsions. Acute administration of pyrithioxine (0.01 g/kg) after cessation of the intoxication period did not mitigate the withdrawal symptoms, and massive amounts (2 g/kg) killed the animals within a few hours. Voluntary alcohol consumption of Alko AA rats ( a high-consumer strain) was not altered by pyrithioxine. The results indicate that pyrithioxine may affect the symptoms of ethanol withdrawal in different ways, the effect depending on both dose level and time of administration. It is suggested that the reason for the slight beneficial effect of pyrithioxine on the withdrawal symptoms when taken regularly in combination with ethanol is the slight protection afforded against intoxication.
Animals↗
Concentrations of D-glucaric acid in human urine after repeated administration of pyrithioxine.
The urinary excretion of D-glucaric acid in 16 healthy male volunteers, 24 to 66 years of age, was 44 +/- 3 mumol/24 h (25 +/- 2 mumol D-glucaric acid/g creatinine/24 h). Six healthy female volunteers aged 25 to 60 years excreted 42 +/- 5 mumol D-glucaric acid/24 h (30 +/- 3 mumol D-glucaric acid/g creatinine/24 h) in the urine. (The values given are means +/- s.e.m.) In 3 male subjects, daily i.v. infusion of 5 mg pyrithioxine in 3 ml physiol. saline/kg body weight on 5 successive days produced a slight increase in the daily renal excretion of D-glucaric acid during the 5-day period. The increase was reversible during the next few days. Oral doses of 200 mg pyrithioxine, given three times daily over a period of 4 weeks to 5 female subjects caused a slight increase in the renal excretion of D-glucaric acid/24 h. In the course of the following week, there was a return to baseline levels. The pyrithioxine-associated increase in urinary D-glucaric acid is attributed to its enhanced metabolic formation in the body and indirectly reflects a weak inductive action of pyrithioxine on the hepatic microsomal enzyme system in man. With the evidence on hand, this effect, though slight in extent, would appear to predict no risk of a pharmacokinetic interaction between pyrithioxine and other drugs.
Administration, Oral↗
N1--P2 component of the auditory evoked potential during alcohol intoxication and interaction of pyrithioxine in healthy adults.
The auditory evoked potential was used to assess the effect of alcohol intoxication (1 g/kg) and pyrithioxine (7 mg/kg) on 9 adult subjects. Its components in the latency range 50--250 msec (N1--P2) were studied for 6 g 30 min, during a constant level of alertness. Four periods were considered: alcohol alone, alcohol plus pyrithioxine, pyrithioxine plus alcohol and placebo. With alcohol alone the N1--P2 amplitude was small in the first part of the test and large in the second part as compared to placebo values. Pyrithioxine antagonism was greatest after alcohol had been resorbed. The placebo period indicated that amplitude changes were not due to long-term habituation, when the subject was kept alert.
Adult↗
Facilitation through hyperventilation of therapeutic effect of pyrithioxin in cerebral infarct patients.
A method of treatment consisting in administration of a neurodynamic drug, pyrithioxin, combined with a short period of hyperventilation (HV) was applied in cerebral infarct patients with hemiplegia. The combination was superior to pyrithioxin alone for the motor recovery of these patients. In some cases, it induced immediately a partial restoration of motility. The combination constantly brought about an increase in urinary excretion of norepinephrine and vanilmandelic acid, which failed to occur after pyrithioxin or HV alone. HV appears to facilitate the neural effects of the drug by promoting its transfer into the CNS.
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Clinical evaluation of GABA in the treatment of cerebrovascular disorders. Multi-center double-blind study in comparison with pyrithioxine and placebo.
The therapeutic efficacy of GABA was compared with pyrithioxine and placebo in 432 patients with cerebrovascular disorders by a multi-center (50 hospitals) double-blind clinical trial. 12 tablets (3 g) of GABA and 3 tablets (600 mg) of pyrithioxine were given daily for 8 weeks. Subjective complaints, neurological and psychiatric findings, activity of daily living were checked at the 4th and 8th weeks after medication. The global improvement rates in GABA-treated groups were 59% and 70% each after 4 and 8 weeks of medication, and were significantly superior to the other two groups. Especially on cerebral arteriosclerosis GABA was more effective than the other two drugs, with statistical significance. As for improvement rates of symptoms there were significant differences between GABA and the other two drugs in subjective complaints and in psychiatric findings. The incidence of side effects was 5%, 20% and 8% in GABA, pyrithioxine and placebo, respectively. The incidence of abnormal laboratory data was 2% (3 cases), 8% (11 cases) and 4% (6 cases), respectively. Those in GABA group were transient and restored to normal values after the trial. It is concluded from these results that GABA is safe and effective in the treatment of cerebrovascular disorders.
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[Autoradiographic studies on the distribution of 3H-pyrithioxine in monkey and mouse (author's transl)].
Monkeys and mice received oral and i.p. doses of 3H-labelled pyritinoldihydrochloridemonohydrate (3H-pyrithioxine; Encephabol) and the distribution of radioactivity in the brain and in other organs was investigated by autoradiography. The heaviest label accumulation was present in the pituitary gland. In the monkey the distribution of radioactivity in the brain and in the submandibular gland was different from the distribution found in these organs in the mouse, which may be attributed to the different radioactive metabolites of pyrithioxine produced by the two animal species. Prior to elimination from the body pyrithioxine was completely transformed into metabolites.
Administration, Oral↗
The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life.
Low protein (LP) or low calorie (LC) dietary regimens were applied in early postnatal life(1st-40th day of life) in male rats. After nutritional rehabilitation, open-field behavior in larger more illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), dyadic interactions, and learning ability were investigated in these animals as adults (between the 200th to 300th day of life). LP malnutrition induced an increase of open-field activity with features of sterotypy both in LI and HI situations, an increase number of intersignal reactions during learning procedures without changes in other registered criteria of learning ability (latency, number of correct responses), and an increase of aggressive behavior in pair interaction. LC rats revealed only significant inhibition in LI--open-field activity and a slightly increased number in intersignal reactions during avoidance learning. With the aim of preventing previously described long-term deviations in early malnourished rats, some groups of animals with the above-mentioned early calorie or protein deficits were treated with pyrithioxine (Encephabol Merck) or pyridoxine in 10 doses of 40 mg/kg i.p. administered in the period when nutritional rehabilitation was carried out (between the 40th--50th day of life). The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats except the increase of intersignal reactions which was even potentiated. Pyridoxine was less effective but normalized the increase number of intersignal reactions both in LP and LC rats. The effect of pyridoxine of adult LC rats was interesting. There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.
Aggression↗
Increase in acetylcholine concentrations in the brain of 'old' rats following treatment with pyrithioxin (Encephabol).
Treatment of old rats, for two to three weeks, with pyrithioxin led to an increase in the levels of endogenous acetylcholine (ACh) in the cortex and the striatum but not in the hippocampus. Pretreatment of old rats with pyrithioxin also increased the resting release and the K+ stimulated release of radioactive ACh from brain slices in vitro.
Acetylcholine↗
[Pyrithioxine: a new basic treatment of rheumatoid arthritis. Open study of 60 cases with a follow-up of 6 months].
Pyrithioxine, a chemical compound with several points in common with penicillinamine, was used for six months as the basic treatment in a series of 60 cases of rheumatoid arthritis, in a dose of 600 mg per day. The results were favourable in 60 per cent of cases, with a marked fall in articular index, a return to normal of sedimentation rate and, less commonly, negativisation of the Rose-Waaler reaction. Side effects were essentially cutaneo-mucosal (pruitus, rash) and necessitated the interruption of treatment in 16.5 per cent of cases. No complications were seen. Compared with penicillinamine, pyrithioxine appears to be less effective but better tolerated. The place of this new basic drug in the basic treatment of rheumatoid arthritis remains to be precisely determined.
Adult↗
[Pyrithioxine a new basic treatment of rheumatoid polyarthritis: initial study of 72 cases with a 6-month follow-up].
Pyrithioxine has certain chemical resemblances to penicillamine and is used as original treatment in a series of 72 cases of rheumatoid arthritis over a period of six months in a dose of 600 mgs daily. Results were favourable in 63% of cases with important lowering of the articular index, return to normal of the sedimentation rate and less frequently a reversal of the Waaler-Rose reaction. Secondary complications were essentially muco-cutaneous, sometimes gastric and necessitated stopping treatment in 15% of cases. No other serious side effect has been observed. When compared with penicillamine pyrithioxine would appear less efficacious but better tolerated. The usefulness of this new medicament in the treatment of rheumatoid arthritis needs to be further explored.
Adult↗
[Study of 70 cases of rheumatoid polyarthritis treated by pyrithioxin with a 1-year follow-up].
The authors present their own series of 70 rheumatoidpolyarthritis cases treated with pyrithioxine during one year or more except in the case of failure or intolerance. The following results were observed after one year: 54 percent showed positive results, 34 percent showed no results or dubious ones, and there was 13 percent of discontinuance because of intolerance. Modifications of the posology and methods of administering are proposed, and the role of pyrithioxine, as a basic treatment for rheumatoid polyarthritis, is discussed.
Adult↗
The influence of pyrithioxine on certain factors of intelligence1.
A double-blind trial with pyrithioxine was made with 22 pairs of visually handicapped children who were equal in IQ scores and in chronological age. Although an improvement of abstraction ability was noticed, the overall results were not in concurrence with the general tendency in relevant literature.
Achievement↗
The use of pyrithioxine in a group of visually handicapped children. A preliminary report from the School for the Blind, Worcester.
A double-blind trial with pyrithioxine (Encephabol) was made witn 22 pairs of visually handicapped subjects who were equal in IQ scores and in chronological age. Although an improvement of abstraction ability was noticed, the over-all results were not in concurrence with the general tendency in relevant literature. A follow-up cross-over study is suggested.
Adolescent↗
[Pyrithioxin and rheumatoid polyarthritis].
After reviewing the literature, the authors demonstrate that pyrithioxine is active in rheumatoid arthritis. The effectiveness is marked by a 50 per cent reduction in the articular index in 59.7 per cent of cases, a reduction in the duration of morning stiffness in 49 per cent of cases, a decreased erythrocyte sedimentation rate in 52.4 per cent of cases and a statistically significant decrease in the mean of these parameters in relation to the mean value at the beginning of treatment. The good results were considered to be those cases in which two of the three criteria (articular index, morning stiffness and erythrocyte sedimentation rate) were decreased by at least 50 per cent. Secondary escapes from treatment (13 per cent) and suspension of treatment for intolerance were considered to represent treatment failures. A good result was obtained in 42.7 per cent of cases. Side effects were observed in 40.1 per cent of cases and were responsible for suspension of treatment in 22.8 per cent of cases. Half of the side effects consisted of muco-cutaneous reactions which generally appeared early and were benign. Haematological, renal and gastrointestinal effects and aguestia occurred more rarely. However, a number of patients died as a result of agranulocytosis, hepatitis or extramembranous glomerulonephritis.
Agranulocytosis↗
[Retrospective study of the effects of D-penicillamine and pyrithioxin in the treatment of rheumatoid arthritis].
The authors made a comparative study of the effectiveness and tolerance of D-penicillamine (DP) and pyrithioxine (Pyr) and investigated possible prognostic factors for the tolerance and effectiveness of these two treatments. This retrospective study concerned 150 patients with rheumatoid arthritis (RA). 86 patients were treated with DP and 64 were treated with Pyr. The percentage effectiveness, evaluated in terms of morning stiffness and the articular index as well as the need for steroidal and non-steroidal anti-inflammatory agents, attained 67.4 p. cent with DP and 51.6 p. cent with Pyr. Suspension of treatment because of ineffectiveness, was more frequent with Pyr. The changes in the following laboratory parameters were also compared: ESR, rheumatoid serology, ANF, C3 and C4 complement levels, IgG, IgA and IgM levels. The treatment was stopped definitively because of intolerance in 37.2 p. cent of cases with DP and in 29.7 p. cent of cases with Pyr. Serious renal and haematological complications are essentially, but not exclusively, due to DP.
Arthritis, Rheumatoid↗
Pyrithioxine and thiopronine: new penicillamine-like drugs in rheumatoid arthritis.
Two new SH-CH3-containing drugs have been studied as penicillamine-like agents. Pyrithioxine--retrospectively compared to a D-penicillamine series--was associated with fewer side effect-related withdrawals (14 vs 39) but with more non-responses and withdrawals for relapse. A review of the literature shows that thiopronine and D-penicillamine have a similar "score" of side effects and good responses. More extensively-controlled trials are needed for a better assessment of these new drugs.
Adult↗
Agranulocytosis associated with pyrithioxine therapy.
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