Hypnotics, sedatives and antipsychotics

DARK Classics in Chemical Neuroscience: Methaqualone

“…In the same study, it was determined that methaqualone ( 1 ) is 67% absorbed after 1 h and 99% absorbed after 2 h . Methaqualone ( 1 ) is 75% protein bound in plasma . For the Mandrax formulation of methaqualone ( 1 ), a study revealed that the addition of diphenhydramine did not alter blood plasma levels or bioavailability of the drug …”

“…38 In the same study, it was determined that methaqualone (1) is 67% absorbed after 1 h and 99% absorbed after 2 h. 38 Methaqualone (1) is 75% protein bound in plasma. 39 For the Mandrax formulation of methaqualone (1), a study revealed that the addition of diphenhydramine did not alter blood plasma levels or bioavailability of the drug. 40 Through analysis of blood plasma concentrations of methaqualone (1), following oral administration of a dose at 4 mg/kg, the following half-lives for the drug were determined: during distribution (α) phase, half-life has been reported between 2 and 6 h; during the elimination (β) phase the half- life increases to between 19.6 and 41.5 h; during terminal elimination the half-life ranges between 20 and 42 h. 38,41,42 Studies using 2-C-14-methaqualone have revealed that the drug is taken up rapidly by fatty tissues, the liver, and the brain and excreted slowly through urine, bile, and feces.…”

“…Methaqualone ( 1 ) binds at the transmembrane β+/α– GABA A R subunit interface, a similar binding pocket to the commonly used short-acting intravenous anesthetic etomidate ( 16 ) (Figure ), a known native GABA A R PAM. , Though the activities of methaqualone ( 1 ) and barbiturates have been described as similar (both are hypnosedatives), barbiturates bind in a different allosteric pocket (the β-subunit interface) (Figure ). ,, Ethanol is also thought to act as a GABA A R PAM, but its binding site is not definitive, especially at low concentrations. , Many individuals concurrently used methaqualone ( 1 ) with ethanol to experience enhanced sedative–hypnotic effects. ,, Currently, it is unknown if the mechanisms of these augmented effects are a result of receptor level or pharmacokinetic interactions. One study, looking at simultaneous administration of ethanol and methaqualone in rat, demonstrated increased plasma concentrations and increased uptake of the drug to lipoid tissues such as the brain …”

“…48,60 Though the activities of methaqualone (1) and barbiturates have been described as similar (both are hypnosedatives), barbiturates bind in a different allosteric pocket (the β-subunit interface) (Figure 2). 39,48,50 Ethanol is also thought to act as a GABA A R PAM, but its binding site is not definitive, especially at low concentrations. 61,62 Many individuals concurrently used methaqualone (1) with ethanol to experience enhanced sedative−hypnotic effects.…”

Evaluation of Emit® Tox Benzodiazepine and Barbiturate Assays on the Vitalab Viva Analyser and FPIA on the Abbott ADx Analyser

“…From a pharmacological point of view (6)(7)(8), benzodiazepine and barbiturates are used as antidepressants, anxiolytic, anticonvulsant, hypnotic, muscle relaxant, and preanesthetic drugs (midazolam). Some of them are also frequently detected in blood specimens after acute intoxications (9,10).…”