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.
D000818:Animals; D001835:Body Weight; D004573:Electrolytes / Q000097:blood; D000431:Ethanol; D006801:Humans; D008297:Male; D011736:Pyridoxine / Q000008:administration & dosage; D011746:Pyrithioxin / Q000494:pharmacology; D051381:Rats; D012640:Seizures; D013016:Sound; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D004573:Electrolytes; D000431:Ethanol; D011746:Pyrithioxin; D011736:Pyridoxine