Acute neurotoxicity associated with recreational use of methylmethaqualone confirmed by liquid chromatography tandem mass spectrometry

Abstract

Methylmethaqualone is a sedative designer drug created by adding a methyl group to the 3-phenyl ring of methaqualone, and is at present not subject to restrictive regulation in many countries. To our knowledge, no case of methylmethaqualone abuse has been published to date in the scientific literature, and the only sources of information are users' reports on Web discussion forums and data from preclinical animal studies. We report a case of oral methylmethaqualone abuse confirmed by liquid chromatography tandem mass spectrometry in a 24-year-old previously healthy Caucasian male. Observed symptoms and signs such as central nervous system depression alternating with excitation, psychomotor agitation, muscle hyperactivity, and tachycardia were compatible with methaqualone-induced adverse effects. Except for the mild tachycardia (115 beats/min), other vital signs were normal: blood pressure 134/89 mmHg, body temperature 36.2°C (97.16°F), and peripheral oxygen saturation 99% while breathing room air. The ECG showed no prolongation of the QT interval and the QRS duration was normal. Laboratory analysis revealed a slight increase in creatine kinase (368 U/L) and alanine aminotransferase (90 U/L) serum concentrations. Blood alcohol concentration was 0.32 g/L. Methylmethaqualone was identified in a serum sample collected on admission which was analyzed by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction. After a few days the patient ingested the same amount of substance with identical symptoms. Based on the chemical structure and animal data, and according to this case report and users' Web reports, methylmethaqualone appears to have a similar acute toxicity profile to methaqualone, with marked psychomotor stimulation. Symptoms of acute toxicity can be expected to resolve with supportive care. The paper is written in US EnglishRunning head: Acute neurotoxicity after methylmethaqualone abuse. Keywords:drug of abuse, designer drug, methaqualone, acute toxicity. Number of references: 20 Figures: 2 AbstractMethylmethaqualone is a sedative designer drug created by adding a methyl group to the 3-phenyl ring of methaqualone, and is at present not subject to restrictive regulation in many countries. To our knowledge, no case of methylmethaqualone abuse has been published to date in the scientific literature, and the only sources of information are users' reports on Web discussion forums and data from preclinical animal studies. We report a case of oral methylmethaqualone abuse confirmed by liquid chromatography tandem mass spectrometry in a 24-year-old previously healthy Caucasian male. Observed symptoms and signs such as central nervous system depression alternating with excitation, psychomotor agitation, muscle hyperactivity, and tachycardia were compatible with methaqualone-induced adverse effects. Except for the mild tachycardia (115 beats/min), other vital signs were normal: blood pressure 134/89 mmHg, body temperature 36.2°C (97.16°F), perip...

DARK Classics in Chemical Neuroscience: Methaqualone

“…The patient was found by relatives in a confused and agitated state experiencing severe psychomotor agitation, generalized clonic muscle contraction, and urinary incontinence. 105 Midazolam (10 mg) was administered by paramedics to decrease these symptoms. The patient was then admitted for overnight observation and discharged the following day.…”

“…After 2 h of observation, the patient was discharged and referred to a psychiatrist. 105 The dichloride analogue SL-164 (18b), also known as dicloqualone, developed in 1960 by Sumitomo Chemical Co., Ltd., Osaka, Japan, has been mentioned at least twice in the literature in the past two years. 13,14 In 2021, a 22-year-old patient presented to a hospital in Munich, Germany, with prolonged agitated delirium, myocloni, tachycardia, and subfebrile temperature after ingestion of opium poppy tea and 18b.…”

“…Ten days later the same patient repeated the same dosage of ( 18a ) and was brought back to the hospital following administration of midazolam (15 mg) by paramedics. After 2 h of observation, the patient was discharged and referred to a psychiatrist …”

“…The first apparent clinical description of methylmethaqualone ( 18a ) was published in the literature in 2012 when a patient from Zurich, Switzerland, ingested two 500 mg tablets for recreational purposes. The patient was found by relatives in a confused and agitated state experiencing severe psychomotor agitation, generalized clonic muscle contraction, and urinary incontinence . Midazolam (10 mg) was administered by paramedics to decrease these symptoms.…”

Anxiolytic/Sedative-Hypnotics

“…As a result of its selective inhibition of polysynaptic spinal reflexes, toxicity is notable for coma plus hyperactive motor dysfunction, clinically manifested as increased muscle tone, hyperreflexia, clonus, and myoclonus [85][86][87]. Another structurally related compound, methyl-methaqualone, has been reported to result in similar clinical effects [88]. It has been suggested that case reports of retinal and gastrointestinal hemorrhage may be explained on the basis of drug-induced effects on platelet dysfunction and coagulation factors [89,90].…”