Mephenaqualone

Mephenaqualone is a quinazolinone sedative-hypnotic and a structural analog of methaqualone, differing by the replacement of the 2-methyl group with a 2-methyl-3-(ortho-methylphenyl) pattern — or in some characterizations, by methylation at the 3-phenyl ring. Like methaqualone, it acts as a positive allosteric modulator of GABA-A receptors, producing sedation, euphoria, muscle relaxation, and disinhibition through a mechanism distinct from classical benzodiazepines in its specific binding profile and receptor subtype interactions.

Mephenaqualone was developed and found limited pharmaceutical application in some countries before being phased out. It has re-emerged in the illicit drug market, most notably in sub-Saharan Africa under the street name "Mandrax" — often referring to tablets containing mephenaqualone that are smoked in combination with cannabis through a modified pipe. This "Mandrax" pattern of use, distinct from the oral tablet use that characterized methaqualone's Western prevalence, is associated with severe respiratory complications from pyrolysis products and contaminated materials.

Like methaqualone, mephenaqualone carries a significant addiction and dependence liability, with a withdrawal syndrome that can include seizures. Its quinazolinone mechanism may produce a somewhat different quality of experience than benzodiazepines — users describe a characteristic "mellow buzz" with euphoria and loss of inhibition that methaqualone users identified as distinctive. The limited community experience in the database and the compound's primary contemporary use pattern in Africa make comprehensive harm reduction discourse limited.