Methanol-Related Deaths in Ontario

Objective: Methanol poisoning accounts for several deaths annually in the province of Ontario. Our study was aimed at identifying the associated epidemiological factors for fatal outcomes following methanol poisoning in order to develop preventative strategies. Methods: The records of the Ontario Provincial Coroner's Office were reviewed retrospectively for all poison-related, alcohol-related, and chronic alcohol use-related deaths for the period of January 1, 1986 to December 31, 1991. Age, gender, reason for ingestion (accidental or intentional), and source of methanol for each victim were recorded. Results: There were 43 fatalities during this period, 39 males and 4 females with a mean age of 45 years (range 18–80). Suicide attempts accounted for 21 (49%) cases while the remaining 22 (51%) deaths were classified as accidental. Fourteen (64%) of these 22 patients consumed products labeled as methyl alcohol or wood alcohol as a substitute for ethanol. In 3 cases, the accidental ingestion was the direct result of methanol being improperly stored in containers normally associated with ethanol. The remaining 5 patients were poisoned through the consumption of liquor from illicit sources. Conclusions: Over half of the methanol-related deaths in Ontario are accidental and potentially preventable. Possible preventative strategies include mandatory product relabeling to eliminate the word alcohol, enhanced public education, and the addition of aversive agents to methanol-containing commercial products.     

INTERACTIONS BETWEEN METHAQUALONE AND ETHANOL IN RATS AND MICE DURING ACUTE AND CHRONIC STATES

1. The effects of acute and chronic treatment of methaqualone on ethanol preference, the rate of disappearance of ethanol and on toxicity were studied in mice and rats. 2. Acute treatment with methaqualone showed a dose-dependent suppression in the voluntary intake of ethanol in C57B1/6J mice and rats. No significant change in ethanol intake was observed during chronic methaqualone treatment and withdrawal. 3. Methaqualone pretreatment significantly (P < 0.005) delayed the disappearance of ethanol in the blood and brain over a period of 50 to 200 min after a loading dose of 2.0 g/kg, i.p., of ethanol. 4. Methaqualone pretreatment at doses of 140 and 200 mg/kg significantly increased ethanol toxicity by 11% and 28%, respectively. Co-administration of ethanol using 6.0, 7.0 and 8.0 g/kg also reduced the LD₅₀ of methaqualone by 19%, 24% and 40%, respectively. 5. Chronic administration with ethanol decreased the toxicity due to methaqualone. Potentiation of ethanol toxicity by methaqualone may be of clinical importance in view of the narrow range of safety margin of ethanol.     

Agents enhancing γ-aminobutyric acid receptor-coupled chloride ionophore function. Effects in a social interaction model of anxiety in the rat

A recently described social interaction (SI) model which is sensitive to single doses of benzodiazepines and novel non-sedative anxiolytic agents has been used. Activities of drugs were compared in both an anxious (animals housed in pairs, tested with a novel partner) and a non-anxious (animals housed in pairs, tested with the cage mate) condition. Diazepam displays a typical anxiolytic response, increasing SI in the anxious but not in the non-anxious condition. This was associated with a decrease in aggression (AGG) and in locomotion (LOCO) at higher doses. Seven agents were tested which are thought to enhance central nervous system γ-aminobutyric acid (GABA)-mediated neurotransmission by increasing the activity of a receptor-coupled chloride ionophore system as a major component of their action. Tracazolate, RL348, methaqualone, etomidate, LY81067, and pentobarbitone all significantly increased SI in the anxious but not the non-anxious condition. In the anxious condition tracazolate and RL348 reduced AGG and all of these compounds except LY81067 reduced LOCO. Methaqualone and etomidate also reduced LOCO in the non-anxious condition. In addition, an agent which reduces GABA function (picrotoxin) significantly reduced SI in already-anxious animals, consistent with its known anxiogenic properties. Picrotoxin also reduced LOCO in both conditions. Phenobarbitone induced a non-specific effect on SI (increased SI in both anxious and non-anxious conditions), as well as reducing AGG in the anxious condition and LOCO in both conditions. These data suggest that agents enhancing GABA receptor-coupled chloride ionophore function possess anxiolytic properties which may be attributed to this activity.     

用HPLC法同时检测生物检材中安眠酮及其2＇－羟甲基代谢物

提取并确认安眠酮的活性代谢物，建立反相ＨＰＬＣ法同时检测生物体液中安眠酮及该代谢物的方法。使用Ｗａｔｅｒｓ高效液相色谱仪，μ－ＢｏｎｄａｐａｋＣ１８径向加压柱，流动相为甲醇：磷酸二氢钠缓冲液（６０：４０），流速１．６ｍｌ／ｍｉｎ，检测波长２３５ｎｍ，利眠宁为内标对安眠酮及活性代谢物进行检测。结果：各组分分离良好，安眠酮浓度在１．０～３５．０ｍｇ／Ｌ（血清）范围内与峰面积呈线性相关，方法平均回收率为１００．１５％，最低检测浓度为１５ｍｇ／Ｌ，其他常用安眠药物对本法均无干扰。结论：本法可同时检测安眠酮及其活性代谢物，并已用于健康志愿者及１名中毒者体液检材的测定，说明可用于临床检测和中毒检案。     

Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine

Summary The metabolism of methaqualone to the glucuronides of 5 C-monohydroxy metabolites and to the N-oxide has been studied in 2 groups of healthy young adults phenotyped as extensive and poor metabolisers of debrisoquine. No significant interphenotype differences were observed with respect to the excretion of any of the 6 metabolites. It is probable that the genetic regulation of the pathways leading to these metabolites is at a locus other than that which is responsible for the regulation of the oxidation of debrisoquine, guanoxan, phenacetin, phenytoin and sparteine.