Recommendation (from TRS)
Substance identification
Brotizolam (CAS 57801-81-7), chemically 2-bromo-4-(o-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-s-triazolo[4,3-a][1,4]diazepine, is also known as Ladormin, Lendorm, Lendormin, Lindormin, Noctilan, Dormex and Sintonal.
WHO review history
Brotizolam was reviewed by the 26th (4) and 27th (5) meetings of the Committee in 1989 and 1990, respectively. It was not recommended for international control because of the absence of evidence concerning its abuse at those times. In 1992, the 28th meeting (6) of the Committee recommended brotizolam for critical review.
Similarity to known substances and effects on the CNS
Brotizolam produces the typical pharmacological effects of benzodiazepines and binds with high affinity to benzodiazepine receptors. A number of studies have demonstrated that brotizolam is a short-acting hypnotic with a mean elimination half-life of 4-5 hours.
Dependence potential
Animal studies show that brotizolam has barbiturate-type effects. It produces mild-to-severe withdrawal symptoms similar to those of alcohol or barbiturates and has some reinforcing effects. The few clinical studies available demonstrate the occurrence of rebound insomnia upon withdrawal of the drug. These findings indicate that brotizolam has a moderate dependence potential similar to other benzodiazepine hypnotics.
Actual abuse and or/evidence of likelihood of abuse
In spite of its pharmacological similarity to other benzodiazepine hypnotics, and its marketing in 18 countries, abuse of brotizolam has been reported only in Germany and Hong Kong. Although there has been some abuse and illicit activity involving brotizolam in Germany, these were not considered serious enough by the German authorities to subject the drug to the additional restrictions which are applicable to controlled substances.
Following its introduction to Hong Kong in 1988, the abuse of brotizolam increased rapidly among young people there, leading to the application of stricter control measures in 1990. The company marketing brotizolam withdrew it from Hong Kong in 1992.
On the basis of the experiences of Germany and Hong Kong, it is assessed that brotizolam has an appreciable abuse liability. The problem may be more acute in situations where prescription requirements are not effectively implemented or are not applicable.
Therapeutic usefulness
Brotizolam is marketed as a hypnotic in 18 countries and is assessed to have a moderate to great therapeutic usefulness.
Recommendation
On the basis of the available data concerning its pharmacological and toxicological profile, dependence potential and likelihood of abuse, the public health and social problems associated with the abuse of brotizolam are assessed to be significant in cases where prescription requirements are not effectively implemented or are not applicable, a situation which exists in many developing countries. On the basis of this and the assessment of its therapeutic usefulness, it is recommended that brotizolam be placed in Schedule IV of the Convention on Psychotropic Substances, 1971.