Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Triclofos (INN, CAS 306-52-5, CAS 7246-20-0 for the sodium salt); chemical name: 2,2,2-trichloroethanol dihydrogen phosphate. No isomeric forms are possible.
Similarity to known substances and effects on the CNS
Triclofos sodium has been classified pharmacologically as a sedative—hypnotic with a profile similar to that of chloral hydrate, a substance to which it is chemically related. Triclofos is rapidly biotransformed to trichloroethanol, a pharmacologically active metabolite of chloral hydrate. Triclofos is more palatable and believed to produce less gastric irritation than chloral hydrate. Triclofos sodium has mostly hypnotic but also sedative actions similar to those of chloral hydrate. The principal effects are sedation at low doses and sleep induction at higher ones. Overdose may cause loss of reflex, respiratory depression, and, occasionally, death.
Dependence potential
In drug discrimination studies triclofos was identified as a benzodiazepine by the rat but not by the baboon. Pigeons, rhesus monkeys, and baboons did not discrimate triclofos as pentobarbital. The substance did substitute for pentobarbital in the dependent rat but itself produced only mild withdrawal symptoms. Selfadministration studies have not been reported. Controlled human dependence studies have not been carried out.
Actual abuse and or/evidence of likelihood of abuse
There were two abuse cases reported in Finland between 1983 and 1985. In the Drug Abuse Warning Network (DAWN) reports from the USA there were twelve mentions of triclofos from emergency rooms and two from medical examiners from 1979 to 1985. Concerning illicit manufacturing and illicit traffic of the substance, no seizures or clandestine laboratories were reported from 53 countries. Triclofos is available on prescription in eight, and under national control in three out of 57 reporting countries. The foregoing evidence as well as the low predicted dependence potential of the substance may indicate a low abuse liability.
Therapeutic usefulness
Triclofos is a hypnotic that is reported to be effective in the treatment of insomnia, and can also be employed as a mild sedative and to premedicate children before surgery. The therapeutic use of this substance has been largely replaced by other more effective drugs. The Committee rated the therapeutic usefulness of triclofos as low.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential, and actual abuse, the Committee rated the likelihood of abuse of triclofos as low. The degree of seriousness of the public health and social problems associated with the substance were also estimated. to be low as was its therapeutic usefulness. The Committee found that there was insufficient evidence that triclofos is 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 the light of this assessment, the Committee did not recommend scheduling of the drug.
Triclofos (INN, CAS 306-52-5, CAS 7246-20-0 for the sodium salt); chemical name: 2,2,2-trichloroethanol dihydrogen phosphate. No isomeric forms are possible.
Similarity to known substances and effects on the CNS
Triclofos sodium has been classified pharmacologically as a sedative—hypnotic with a profile similar to that of chloral hydrate, a substance to which it is chemically related. Triclofos is rapidly biotransformed to trichloroethanol, a pharmacologically active metabolite of chloral hydrate. Triclofos is more palatable and believed to produce less gastric irritation than chloral hydrate. Triclofos sodium has mostly hypnotic but also sedative actions similar to those of chloral hydrate. The principal effects are sedation at low doses and sleep induction at higher ones. Overdose may cause loss of reflex, respiratory depression, and, occasionally, death.
Dependence potential
In drug discrimination studies triclofos was identified as a benzodiazepine by the rat but not by the baboon. Pigeons, rhesus monkeys, and baboons did not discrimate triclofos as pentobarbital. The substance did substitute for pentobarbital in the dependent rat but itself produced only mild withdrawal symptoms. Selfadministration studies have not been reported. Controlled human dependence studies have not been carried out.
Actual abuse and or/evidence of likelihood of abuse
There were two abuse cases reported in Finland between 1983 and 1985. In the Drug Abuse Warning Network (DAWN) reports from the USA there were twelve mentions of triclofos from emergency rooms and two from medical examiners from 1979 to 1985. Concerning illicit manufacturing and illicit traffic of the substance, no seizures or clandestine laboratories were reported from 53 countries. Triclofos is available on prescription in eight, and under national control in three out of 57 reporting countries. The foregoing evidence as well as the low predicted dependence potential of the substance may indicate a low abuse liability.
Therapeutic usefulness
Triclofos is a hypnotic that is reported to be effective in the treatment of insomnia, and can also be employed as a mild sedative and to premedicate children before surgery. The therapeutic use of this substance has been largely replaced by other more effective drugs. The Committee rated the therapeutic usefulness of triclofos as low.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential, and actual abuse, the Committee rated the likelihood of abuse of triclofos as low. The degree of seriousness of the public health and social problems associated with the substance were also estimated. to be low as was its therapeutic usefulness. The Committee found that there was insufficient evidence that triclofos is 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 the light of this assessment, the Committee did not recommend scheduling of the drug.
ECDD Recommendation
Scheduling/control not currently recommended
Link to full TRS
who_trs_761.pdf1.41 MB