Methaqualone

Abstract: The abuse potential of buspirone, a new dopaminergic antianxiety drug, was evaluated by assessing its subjective effects in standard (10 mg) and high (40 mg) doses. These were compared with methaqualone (300 mg), diazepam (20 mg and 10 mg), and placebo in 24 casual recreational sedative users. Addiction Research Center Inventory scales measuring euphoria, sedation, dysphoria, and abuse liability were used as dependent measures. Groups of subjects received all treatments in randomized order in six weekly 4-hour sessions. Compared to placebo, methaqualone caused elevated scores on euphoria, physical sedation, and abuse liability scales compared to placebo, while 40 mg buspirone caused increased physical sedation, increased physical and mental dysphoria, and lower abuse liability scores. Overall, buspirone at 40 mg appeared unlikely to be reinforcing to recreational illicit drug users; the 10 mg dose was not discriminable from placebo or 10 mg diazepam. Diazepam at 20 mg showed some euphoriant effect compared to placebo.

Abstract: The intermittent type of drug action which is desired in hypnotic treatment is fundamentally different from those types of drug treatment where a constant effect is required. Thus, in insomnia, drug action should be restricted to the duration of the night and residual effects should be absent during day-time. During daily administration there should be no accumulation of the drug. These factors taken together, mean that a rapid rate of elimination is of advantage for a hypnotic. In addition, the patient taking a hypnotic expects that sleep is readily obtained and therefore biopharmaceutical factors, especially those promoting a rapid rate of absorption, are crucial for hypnotic drug formulations. Many barbiturates have a relatively long elimination half life, except methohexitone, hexobarbitone and cyclobarbitone. The traditional classification of barbiturates into long-, intermediate-and short-acting compounds bears no relation to the rale of elimination in humans, and for this and other reasons, should be abandoned. Barbiturate salts are rapidly absorbed, in contrast to the free acids. Liver disease tends to decrease the elimination rate of these compounds, whereas renal insufficiency may give rise to accumulation of polar metabolites (e.g. hydroxyamylobarbitone). Methaqualone, too, has a long elimination half life, so that accumulation may occur during daily administration. Absorption of this compound appears to be quite rapid from the formulations investigated. Although the benzodiazepines nitrazepam and flurazepam are the most frequently used hypnotics today, information concerning their pharmacokinetics in humans is very limited. The elimination half life of nitrazepam is between 18 and 34 hours, whereas that of unchanged flurazepam has not been accurately determined. However, the N-desalkyl metabolite of flurazepam, which has pharmacological properties comparable to the parent drug, has an elimination half life of 2 to 4 days. Substantial accumulation of this metabolite occurs during daily administration of flurazepam. The active metabolite of chloral hydrate (trichloroethanol) is quite rapidly eliminated (t1/2 = 7 to 10h), whereas another important metabolite (trichloroacetic acid, t1/2 = 4 to 5 days) gives rise to substantial accumulation during chronic administration. The potential protein binding displacement interaction of this compound with coumarin oral anticoagulants such as warfarin, should always be considered in clinical practice.

Abstract: WE PREVIOUSLY reported that altered sleep patterns occur during the administration and following withdrawal of glutethimide (Doriden), methyprylon (Noludar), and pentobarbital (Nembutal). 1 The clinical problems associated with these alterations, such as unpleasant dreams, nightmares, drug dependency, and insomnia, were also discussed. These studies suggested that further investigation of the effects of other drugs would be necessary in order to find hypnotics which did not result in sleep alterations and adverse clinical disturbance. Preliminary findings suggested that the nonbarbiturate hypnotics chloral hydrate (Noctec), 2 flurazepam (Dalmane) , 3,4 and methaqualone (Quaalude) 5 might fulfill these requirements. We decided, therefore, to systematically study each of these hypnotic drugs. Methods Subjects were male, 20 to 30 years of age without any medical illnesses, allergies, drug use, or sleep disturbance. During the experiment they were instructed to continue to abstain from using any drugs, including alcohol, to maintain their usual level of physical

Abstract: Some 2-(fluoromethyl) analogues of 2-methyl-3-aryl-4-(3H)-quinazolinones have been synthesized and screened for CNS activities. It was shown that the 2-(fluoromethyl) analogues possess in general more potent CNS depressant activities and less toxicities than their parent compounds. Of particular interest were the 2-(fluoromethyl) analogues (22, 24, and 31) of methaqualone and 6-aminomethaqualone. Compound 24 was more potent in CNS depressant activity and less toxic than methaqualone. Compound 31 exhbited potent central muscle relaxing activity and markedly reduced toxicity as compared with 6-aminomethaqualone.