COMBINED CANNABIS/METHAQUALONE WITHDRAWAL TREATED WITH PSYCHOTROPIC ANALGESIC NITROUS OXIDE

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following the abuse of methaqualone combined and smoked with cannabis. Smoked methaqualone combined with cannabis is called “white pipe” (WP). South Africa is the only country in the world where WP is a major form of substance abuse. This article demonstrates in 101 consecutively treated patients given placebo (100% oxygen) followed by PAN that this therapy produced a measurable therapeutic effect (more than 50% improvement) in 87 patients. This study confirms that WP is a form of substance abuse confined mainly to young adult male subjects.     

Long-term urinary excretion of methaqualone in a human subject

The urinary excretion rates of methaqualone and of one of its metabolites, 6-hydroxymethaqualone (free and conjugated), were determined in a normal male subject over a 30-day period by stable isotope dilution analysis using field ionization mass spectrometry. The excretion rates for methaqualone were fitted by computer to three-and four-exponential functions. The estimated terminal halflife for the drug was approximately 74 hr. 6-Hydroxymethaqualone excretion in the elimination phase was fitted to a single exponential decay curve. Estimated halflives obtained for the free and total (primarily conjugated) metabolite were 78 and 70 hr, respectively. The apparent difference between the latter two values was not statistically significant. The close similarity between the halflives of methaqualone and 6-hydroxymethaqualone indicates that elimination of these compounds is ratelimited by the same pharmacokinetic process. A similarly long halflife, 50 hr, was estimated in a previous study (5) of another subject in which excretion of the compounds was followed over an 11-day period. These results demonstrate that the half-life of methaqualone can be much longer than has been indicated by relatively short-term investigations.Supported by Contract DADA17-73-C-3063 from the U.S. Army Medical Research and Development Command.     

Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose

Summary The urinary excretion of fiveC-monohydroxy metabolites and theN-oxide metabolite of methaqualone in the 24h period immediately after oral dosing with 250 mg methaqualone (Melsed) has been measured in nineteen healthy adults (13 male, 6 female) to assess interindividual variations and in five adults (3 male, 2 female) on five separate occasions to assess intraindividual variations. The overall importance of the six metabolites was 4-hydroxy > $$ " align="middle" border="0"> N-oxide > $$ " align="middle" border="0"> 2-hydroxymethyl > 3-hydroxy > 6-hydroxy = 2-hydroxymethyl. Variations in this order both within the 24h period and within each of the three eight-hour periods constituting the 24 hours were minor and variations in the absolute amount of each metabolite excreted ranged from two to three-fold. Intraindividual variations were generally smaller than interindividual variations and for each individual the pattern of metabolism was similar on the five occasions. There is evidence that theC-oxidation of methaqualone may be more sensitive to cyclical variations in hormone levels than isN-oxidation.     

HPLC同时测定人血清中4种非苯二氮(艹卓)类镇静催眠药物

目的　建立一种同时测定多种非苯二氮类镇静催眠药物的方法 ,用于临床中毒的定性与定量分析。方法　血样用乙醚一步萃取 ,二极管阵列检测器检测 ,波长为 2 5 4nm ,采用外标法 ,对血样中的佐匹克隆、扎莱普隆、唑吡坦、甲喹酮进行定性与定量分析。结果　血浆中 0 .1～ 2 μg·mL-1浓度范围内具有良好的线性关系 ,血浆回收率均大于 90 % ,日内、日间RSD均小于 10 %。结论　本方法简单、灵敏、准确、干扰小 ,适用于低浓度生物样本的测定。     

口服氯硝西泮治疗失眠27例

氯硝西泮是苯并二氮杂(艹卓)类衍生物,有抗惊厥和镇静的作用,本文用氯硝西泮与甲喹酮对46例失眠病人进行了对照研究,氯硝西泮组有效率达81％,其效果优于甲喹酮,在服用过程中,未见明显副反应。结果表明:氯硝西泮是一种有效的安眠镇静药。     

GC—MS定性定量分析生物检材中的安眠酮

目的：建立定性定量检测人体尿液、血液及唾液中安眠酮的分析方法。方法：尿液、血液、唾液等生物样本中的安眠酮经固相萃取法进行提取后,用气相色谱-质谱仪进行定性定量分析,从线性、抗干扰性、精密度、回收率及稳定性等方面对方法进行验证。结果：安眠酮浓度在0—400．0ng·mL^-1的范围内线性良好（r≥0．999）,方法的最低检出量为8．0ng·mL^-1;最低定量限为100．0ng·mL^-1;方法的日内、日间精密度CV≤5％（n=6）;各基质中前处理回收率在±10．0％（n=3）范围内。结论：本方法检测准确、灵敏、特异性好,可满足尿液、血液、唾液等生物检材中安眠酮的定性定量分析。     

Effects of dixyrazine and methaqualone on the sleep pattern in normal man

Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox^® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox^® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.     

Methaqualone pharmacokinetics after single- and multiple-dose administration in man

Serum levels of methaqualone (MTQ) were determined in eight unfasted subjects following single- and multiple-dose administration of 1×300 mgtablet over a 28-day period. Data were analyzed by a two-compartment open model. Following a fairly rapid absorptive phase (K _a =0.82±0.32 hr^–1),the serum elimination curve was biexponential, consisting of a phase predominantly due to distribution (=0.97±0.55 hr^–1)and a phase predominantly due to elimination (=0.036±0.004 hr^–1).A steady-state MTQ serum concentration profile was observed within the first week. There were no significant changes in the kinetics of absorption, distribution, or elimination over the 28-day period of drug administration. Urinary D-glucaric acid excretion, which increased two-to threefold after the first week of MTQ dosing, returned to normal levels when the drug was discontinued. The significance of the pharmacokinetic parameters in relation to bioavailability and biological disposition of single and multiple dose MTQ administration is discussed.     

Enhancement of benzodiazepine binding by methaqualone and related quinazolinones

Methaqualone and mecloqualone were found to inhibit [³H]diazepam binding to rat cortical membranes, whereas a related quinazolinone, piriqualone (3-(2-methylphenyl)-2-[2-(2-pyridinyl)ethenyl]-4(3H)-quinazolinone), elicited an increase in the binding. Irrespective of their in vitro effects on benzodiazepine binding, all three quinazolinones enhanced the amount of intravenously administered [³H]flunitrazepam bound to mouse brain in vivo. Ex vivo experiments indicated that the enhanced binding induced by methaqualone and piriqualone, as well as that elicited by the pyrazolopyridine binding enhancers cartazolate and tracazolate, involved an increase in receptor density. This ex vivo effect differed from the in vitro enhancement of [³H]diazepam binding by piriqualone, cartazolate, and tracazolate, which was caused by an increase in binding affinity, and the in vitro inhibition of binding by methaqualone. The quinazolinones did not appear to affect [³H]GABA binding, but GABA-like activity was suggested by their potent reversal of the cerebellar cyclic GMP accumulation induced by isoniazid. The benzodiazepinelike actions (anticonvulsant, hypnotic, anxiolytic) exerted by methaqualone and related quinazolinones may be mediated via GABA/benzodiazepine/barbiturte receptor complexes.     

HPLC同时测定人血清中4种非苯二氮苯卓类镇静催眠药物

 目的建立一种同时测定多种非苯二氮类镇静催眠药物的方法，用于临床中毒的定性与定量分析。方法血样用乙醚一步萃取，二极管阵列检测器检测，波长为254nm，采用外标法，对血样中的佐匹克隆、扎莱普隆、唑吡坦、甲喹酮进行定性与定量分析。结果血浆中0.1～2 μg·mL^-1浓度范围内具有良好的线性关系，血浆回收率均大于90%，日内、日间RSD均小于10%。结论本方法简单、灵敏、准确、干扰小，适用于低浓度生物样本的测定。