Carbromal

Substance identification
Carbromal (INN, CAS 77-65-6), chemically, N-(aminocarbony]l)-2-bromo-2-ethylbutanamide, is also known as bromadalum (Ph. Helv. V.), bromdiaethylacetylcarbamidum (OeAB IX), bromodiethylacetylurea (Ph. Jap. 1961), carbromalum (Ph. Helv. VI). No isomeric forms are possible.

Similarity to known substances and effects on the CNS
Acecarbromal has been classified as a non-barbiturate sedative-hypnotic with a profile similar to that of glutethimide. In single doses the substance produces barbiturate-like sedative-hypnotic effects. Dose-related drowsiness, vertigo, confusion, and motor incoordination can occur. After prolonged use, the pharmacological profile becomes more like that of bromide

ion. Chronic bromism leads to signs and symptoms such as loss of memory, confusion, inability to concentrate, hallucinations (both transitory and prolonged), delusions, and delirium, which are often presented as other severe psychiatric disturbances. Indeed, until bromism was recognized as a toxicological syndrome, it accounted for a large number of admissions to psychiatric hospitals. Carbromal, like the barbiturates, is metabolized by hepatic microsomal enzymes and probably stimulates the production of: these enzymes. It should be pointed out that this may increase the range of toxicological effects, owing to the production of increasing amounts of bromide ion.

Dependence potential
In drug discrimination studies carbromal was identified as pentobarbital-like by the pigeon, but only partially by the rhesus monkey. The substance showed little evidence of barbiturate-like physical dependence in the rat intraperitoneal infusion model. It should be noted, however, that doses were low relative to pharmacodynamic doses because of difficulties in dissolving the substance. In self-administration studies in the pentobarbital-trained rhesus monkey, carbromal was marginal in two animals and positive in one at only one dose level. It was self-administered in only one of three monkeys when substituted for cocaine. The results indicate that carbromal is only marginally self-administered. There are no reported controlled human dependence studies.

Actual abuse and or/evidence of likelihood of abuse
There was a-significant level of-abuse of carbromal in the Federal Republic of Germany in the mid-1970s. Since 1978, abuse has been seen only sporadically and at a rather low level. Belgium reported some abuse of carbromal in 1981 and seven cases were reported in Finland from 1983 to 1985. Data on national control was available for 59 countries. The drug is under national control, at least at the prescription level, in seven countries. A small-number of seizures or diversions were reported by Finland, USA and the Federal Republic of Germany. No illicit manufacture or traffic was reported.

Therapeutic usefulness
Carbromal has been used as a ‘sedative-hypnotic alone and in a variety of combination products. Carbromal is known to be marketed in Finland, France, the Federal Republic of Germany, and Switzerland. The drug appears in several pharmacopoeias and may be widely used in generic drugs. The therapeutic use of this substance has been -largely replaced- by other more effective drugs. The Committee rated the therapeutic usefulnesosf carbromal as low.

Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and actual abuse, the Committee rated the likelihood abuse of carbromal as moderate. The degree of seriousness of the public health and social problems associated with the substance was found to be low, as was its therapeutic usefulness. The Committee found that there was insufficient evidence that carbromal is currently being, or is likely to be, abused so as to constitute a public health and social problem warranting the placing of the substance under international control. In light of this assessment, the Committee did not recommend scheduling of carbromal.