Examination of the dependence potential of chloral hydrate by oral administration to normal monkeys.
Chloral hydrate (CAS 302-17-0, Chloraldurat), a widely used hypnotic and sedative agent was investigated on its dependence potential in normal Cynomolgus monkeys following oral administration for 6 weeks. Based on the results of a pilot experiment in this study the maximum therapeutic dose was employed (30 mg/kg b.w./day) and an approximately 3-fold higher dose (100 mg/kg b.w./day). The test substance was administered twice a day at interval of 12 h in order to simulate the worst-case situation. In this study there was no indication for any physical dependence potential following a 6-week treatment period with chloral hydrate at dose levels of 2 x 30 and 2 x 100 mg/kg b.w./day, by gavage. In contrast, the positive control substance flunitrazepam (CAS 1622-62-4) in dose level of 2 x 2 mg/kg b.w./day, by gavage possessed a pronounced physical dependence potential. During the withdrawal period flunitrazepam resulted in am impaired motor coordination, tremor, hyperirritability, restlessness and - occasionally - grimacing, an impaired perception, convulsions, emesis and increased body temperature lasting for approximately 7 days after the last application. Symptoms were most pronounced 12 h after the last application (theoretically the next application).
Leuschner
J
J
LPT Laboratory of Pharmacology and Toxicology, Hamburg, Germany.
Zimmermann
T
T
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects; D002697:Chloral Hydrate; D005445:Flunitrazepam / Q000009:adverse effects; D006993:Hypnotics and Sedatives; D008252:Macaca fascicularis; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000209:etiology*
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D002697:Chloral Hydrate; D005445:Flunitrazepam