EXAMINATION OF THE DEPENDENCE POTENTIAL OF CHLORAL HYDRATE BY ORAL-ADMINISTRATION TO NORMAL MONKEYS

Chloral hydrate (GAS 302-17-0, Chloraldurat(R)), a widely used hypnoti c and sedative agent was investigated on its dependence potential in n ormal Cynomolgus monkeys following oral administration for 6 weeks. Ba sed on the results of a pilot experiment in this study the maximum the rapeutic 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 administ ered twice a day at an interval of 12 h in order to simulate the worst -case situation. In this study there was no indication for any physica l dependence potential following a 6-week treatment period with chlora l hydrate at dose levels of 2 x 30 and 2 x 100 mg/kg b.w./day, by gava ge. In contrast, the positive control substance flunitrazepam (GAS 162 2-62-4) in a dose level of 2 x 2 mg/kg b.w./day, by gavage possessed a pronounced physical dependence potential. During the withdrawal perio d flunitrazepam resulted in an impaired motor coordination, tremor, hy perirritability, restlessness and occasionally - grimacing, an impaire d perception, convulsions, emesis and increased body temperature lasti ng for approximately 7 days after the last application. Symptoms were most pronounced 12 h after the last application (theoretically the nex t application).