2-Methyl-3-(2-methylphenyl)-4(3H)-chinazolinon

DEA NFLIS-Drug Category -> Depressants and Tranquilizers

DEA Schedule I Controlled Substance -> Depressants

Pharmaceuticals -> Hypnotics

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

CRYSTALS

White or almost white, crystalline powder.

PRACTICALLY INSOL IN WATER

Soluble 1 in 12 parts of alcohol, 1 in 1 part of chloroform, and 1 in 50 parts of ether.

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P264, P270, P273, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 67 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule I includes methaqualone, DEA Code #2565; Drug class: Depressant.

Congress, in 1984 passed legislation (Public Law 98-329) ... to transfer methaqualone from Scheduled II to Schedule I ... /and/ to withdraw marketing approval for methaqualone. ... Methaqualone was removed from the market in the United States and placed into Schedule I of the Controlled Substances Act.

SEVERE CNS DEPRESSION MAY OCCUR WHEN METHAQUALONE IS TAKEN IN COMBINATION WITH ETHANOL OR OTHER CNS DEPRESSANTS. METHAQUALONE INCREASES THE EFFECTS OF MAO INHIBITORS AND TRICYCLIC ANTIDEPRESSANTS. IN COMBINATION WITH PHENOTHIAZINES AND TRICYCLIC ANTIDEPRESSANTS, IT MAY CAUSE EPISTAXIS AND MENSTRUAL IRREGULARITIES.

TWELVE HEALTHY SUBJECTS RECEIVED THREE SINGLE ORAL DOSES (250 MG) OF METHAQUALONE ALONE OR IN COMBINATION WITH DIPHENHYDRAMINE (25 MG). BLOOD SAMPLES WERE COLLECTED FOR A 48-HOUR PERIOD AFTER EACH DOSE AND ANALYZED FOR METHAQUALONE AND ITS MAJOR METABOLITE, 2-METHYL-3-(2'-HYDROXYMETHYLPHENYL)-4(3H)-QUINAZOLINONE. PEAK BLOOD CONCENTRATIONS RANGING FROM 1.0 TO 2.7 UG/ML OCCURRED APPROXIMATELY 1-2 HOURS AFTER THE ORAL DOSE. DIPHENHYDRAMINE ADMINISTERED AT THE DOSAGE LEVEL USED IN THERAPEUTIC COMBINATION PRODUCTS DID NOT ALTER THE BLOOD LEVELS OF METHAQUALONE OR ITS METABOLITE.

Methaqualone in conjunction with diphenhydramine was strongly suspected of being responsible for a fixed drug eruption in 1 patient.

IN MAN, AFTER 3 WK OF USE IN NORMAL DOSAGE, THERE IS NO SIGNIFICANT CHANGE IN HALF-LIFE OF ANTIPYRINE OR PHENYLBUTAZONE OR IN EXCRETION OF 6BETA-HYDROXYCORTISOL BUT IN HYPNOTIC-DEPENDENT SUBJECTS ANTIPYRINE HALF-LIFE IS MODERATELY SHORTENED, EFFECT BEING LESS THAN IN BARBITURATE DEPENDENCE ... .

DURING SEDATION ... FATIGUE & OCCASIONALLY DIZZINESS & TORPOR MAY OCCUR. WITH HYPNOTIC DOSES THERE MAY BE TRANSIENT PARESTHESIAS PRECEDING ... SLEEP. PERSISTING PARESTHESIAS AND OTHER SIGNS OF PERIPHERAL NEUROPATHY THAT LAST FOR MONTHS TO YEARS MAY OCCUR. OCCASIONALLY, RESTLESSNESS & ANXIETY ARE OBSERVED ... OTHER SIDE EFFECTS INCL XEROSTOMIA, ANOREXIA, NAUSEA, VOMITING, DIARRHEA, EPIGASTRIC DISCOMFORT ... .

MILD OVERDOSAGE USUALLY CAUSES EXCESSIVE CENTRAL DEPRESSION ... WITH SEVERE OVERDOSAGE, DELIRIUM, PYRAMIDAL SIGNS (SUCH AS HYPERTONICITY, HYPERREFLEXIA, & MYOCLONUS) & FRANK CONVULSIONS MAY OCCUR. MYOCLONIC EPISODES & AMNESIA HAVE BEEN REPORTED IN 1 CASE WITH DOSE AS LOW AS 400 MG.

DURING COMA, CARDIOVASCULAR & RESP DEPRESSION ARE LESS SEVERE THAN WITH BARBITURATES. COMA HAS OCCURRED AFTER 2.4 G & DEATH AFTER 8 G.

METHAQUALONE ... HAS BEEN COMMONLY ABUSED BY DRUG-DEPENDENT INDIVIDUALS & LONG-TERM USE OF LARGER THAN USUAL THERAPEUTIC DOSES MAY RESULT IN PSYCHIC & PHYSICAL DEPENDENCE.

For more Human Toxicity Excerpts (Complete) data for METHAQUALONE (19 total), please visit the HSDB record page.

REPEATED ORAL ADMINISTRATION OF METHAQUALONE (100 MG/KG/DAY) TO RATS FOR 6 CONSECUTIVE DAYS EVOKED APPROXIMATELY A 2.5 FOLD INCREASE IN P-NITROPHENOL GLUCURONIDATION BY HEPATIC MICROSOMES.

METHAQUALONE HAD RELATIVELY LOW ACUTE ORAL TOXICITY IN RATS AND MICE AND WAS VERY WELL ABSORBED. IN SUBACUTE TOXICITY STUDIES, IT CAUSED 60% MORTALITY IN RATS AT 130 MG/KG/DAY FOR 30 DAYS, AND 90 MG/KG/DAY CAUSED 21% MORTALITY. IN CHRONIC TOXICITY TESTS, 30 MG/KG/DAY FOR 180 DAYS PRODUCED NO TOXIC SYMPTOMS IN RATS OR DOGS. A SINGLE DOSE OF 70 MG/KG AFFECTED ENERGY METABOLISM BY RAT BRAIN MITOCHONDRIA.

... /In/ rats /fed/ a diet containing 0.8% methaqualone ... double vertebral centra and extra lumbar ribs /were found/ in some of the offspring. ... No teratogenicity /was found/ in rabbits given 200 mg per kg orally from day one through 29 and in rats given 100 mg per kg from day 1 through day 20.

Administration of methaqualone to pregnant rats increased the incidence of cleft palate in the offspring ... .

Immediately attention is directed to preservation of the airway, the respiration, and the cardiovascular status. Tracheal intubation in a comatose patient should be followed by gastric lavage with a large bore tube, activated charcoal, and a cathartic. There is no role for forced diuresis in the elimination of methaqualone, ... . In very severe methaqualone overdose unresponsive to conservative therapy, with plasma levels exceeding 4 mg/dl, hemodialysis, or more preferably sorbent hemoperfusion, has been shown to be effective in reversing coma, reducing plasma levels, and effecting a complete recovery.

Baseline laboratory tests for severe poisonings include a complete blood count, platelets, prothrombin time, electrolytes, glucose, creatinine, liver function tests, arterial blood gases, and electrocardiogram.

As for all sedative-hypnotic overdoses, initial evaluation is directed toward ensuring the adequacy of the ABCs (airway, breathing, and circulation) and administering glucose, naloxone, and thiamine.

Alert patients who ingest more than two times the recommended hypnotic dose and present within 4 hours of ingestion should have ipecac-induced emesis. Obtunded patients with compromised gag reflex should have an endotracheal intubation first and then lavage. Decreased gastrointestinal mobility in coma may result in effective lavage 8 to 12 hours after ingestion. Patients who present more than 4 hours after ingestion of methaqualone and are asymptomatic or minimally symptomatic require no decontamination. Activated charcoal and cathartics should be given at the usual dosge after syrup of ipecac or lavage.

Prolonged hemodialysis and peritoneal dialysis reduce plasma levels (e.g., clearances of 7.5 and 29 ml/min, respectively, in one overdose case), but do not alter clinical outcome significantly. Hemoperfusion has a methaqualone clearance superior to that of hemodialysis (179 ml/min) but clinical response is limited perhaps because of the large volume of distribution and large tissue stores. Blood methaqualone levels over 40 ug/ml suggest the need for hemoperfusion. Forced diuresis is contraindicated because of the propensity of methaqualone to cause pulmonary edema.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule I includes methaqualone, DEA Code #2565; Drug class: Depressant.

Congress, in 1984 passed legislation (Public Law 98-329) ... to transfer methaqualone from Scheduled II to Schedule I ... /and/ to withdraw marketing approval for methaqualone. ... Methaqualone was removed from the market in the United States and placed into Schedule I of the Controlled Substances Act.

N - Nervous system

QN - Nervous system

IN ADDITION TO SEDATIVE-HYPNOTIC PROPERTIES ... /IT/ POSSESSES ANTICONVULSANT, ANTISPASMODIC, LOCAL ANESTHETIC, & WEAK ANTIHISTAMINIC PROPERTIES. IN HIGH DOSES IT SELECTIVELY DEPRESSES POLYSYNAPTIC PATHWAYS IN THE SPINAL CORD. THE DRUG HAS ANTITUSSIVE ACTIVITY COMPARABLE TO THAT OF CODEINE ... IT LACKS ANALGESIC ACTIVITY.

MORE THAN 99% OF THE DRUG IS METABOLIZED BY THE HEPATIC MICROSOMAL SYSTEM, AND 4-HYDROXYMETHAQUALONE AND THE N'-OXIDE ARE THE MAJOR PRIMARY METABOLITES. AT LEAST EIGHT OTHER HYDROXYL METABOLITES ARE FORMED.

YIELDS 3-(3-HYDROXY-2-METHYLPHENYL)-2-METHYL-4(3H)-QUINAZOLINONE, 3-(4-HYDROXY-2-METHYLPHENYL)-2-METHYL-4(3H)-QUINAZOLINONE, & 6-HYDROXY-2-METHYL-3-(O-TOLYL)-4(3H)-QUINAZOLINONE IN MAN. /FROM TABLE/

... METHAQUALONE ... GAVE 2-NITROBENZO-ORTHO-TOLUIDIDE ... AS HUMAN URINARY METABOLITE.

BIOTRANSFORMATION ... WOULD BE EXPECTED TO PROCEED BY HYDROXYLATION, & THIS LARGELY OCCURS IN PRACTICE, WHEN GLUCURONIDES OF ... 2-METHYL-3-(3-HYDROXY-2-METHYLPHENYL)-4(3H)-QUINAZOLINONE, 2-METHYL-3-O-TOLYL-6-HYDROXY-4(3H)-QUINAZOLINONE & 2-METHYL-3-O-TOLYL-8-HYDROXY-4(3H)-QUINAZOLINONE ... EXCRETED IN URINE OF ... RATS.

For more Metabolism/Metabolites (Complete) data for METHAQUALONE (7 total), please visit the HSDB record page.

Methaqualone has known human metabolites that include hydroxy-methaqualone.

IN MAN, 99% OF METHAQUALONE IS ABSORBED IN 2 HOURS. IN THE PLASMA, 70 TO 90% IS BOUND TO ALBUMIN. ... METABOLITES ... ARE MAINLY CONJUGATED AND EXCRETED IN THE URINE, BUT THE 4-HYDROXY METABOLITE IS EXCRETED INTO BILE. THE PHARMACOKINETICS IS THAT OF A TWO-COMPARTMENT SYSTEM, WITH A DISTRIBUTION HALF-LIFE OF LESS THAN 1 HOUR AND AN ELIMINATION HALF-LIFE OF 10 TO 40 HOURS.

AFTER ABSORPTION METHAQUALONE IS TAKEN UP BY ADIPOSE TISSUE & GRADUALLY RELEASED OVER PERIOD OF SEVERAL DAYS. AS IT IS RELEASED IT RAPIDLY UNDERGOES GLUCURONIDE CONJUGATION ... & IS EXCRETED EQUALLY IN URINE & FECES FOR UP TO 6-7 DAYS. IN TOXIC DOSES UNMETABOLIZED METHAQUALONE IS ALSO FOUND IN URINE.

BLOOD & URINE SAMPLES FROM ACUTELY INTOXICATED PATIENT STUDIED. 4 MAJOR MONOHYDROXYLATED METABOLITES FOUND CONJUGATED IN URINE. 2-METHYL-3-[2-(HYDROXYMETHYL)PHENYL]-4(3H)-QUINAZOLINONE FOUND UNCONJUGATED IN URINE & BLOOD.

URINARY EXCRETION OF 5 C-MONOHYDROXY METABOLITES & METHAQUALONE N-OXIDE MEASURED FOLLOWING ORAL ADMIN OF 250 MG TO GERIATRIC PT. TOTAL EXCRETION OF 6 METABOLITES IN 24 HR WAS APPROX ONE-HALF THAT IN GROUP OF YOUNG, HEALTHY ADULTS.

For more Absorption, Distribution and Excretion (Complete) data for METHAQUALONE (10 total), please visit the HSDB record page.

QUAALUDE (LEMMON), SOPOR (ARNAR-STONE). ... METHAQUALONE HYDROCHLORIDE: PAREST (PARKE, DAVIS).

ONE OF THE INGREDIENTS OF AKALON-T, BIPHETAMINE T (OBSOLETE), DRASTINETTEN, GAMMAGRIPPYL, MANDRAX, MERPRODEM, SPASMIPRONT. /METHAQUALONE HYDROCHLORIDE/

Methaqualone hydrochloride (contains 87.5% base) 200-mg capsules (Parest-200, Optimil, Somnafac) 400-mg capsules (Parest-400, Optimil, Somnafac) Combination tablets (Mandrax (250-mg methaqualone, 25 mg diphenhydramine)

4(3H)-Quinazolinone, 2-methyl-3-(2-methylphenyl)-: INACTIVE

... METHAQUALONE (PAREST, QUAALUDE, SOMNAFAC, & SOPOR) & ITS SALTS /ARE LISTED AS SCHEDULE II CONTROLLED SUBSTANCES UNDER COMPREHENSIVE DRUG ABUSE PREVENTION & CONTROL ACT OF 1970/.