Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics

Effects of Diazepam on conditioned continuous avoidance response (CAR), conditioned discriminated avoidance response (DAR) and conditioned suppression (Estes-Skinner procedure) were investigated. As the diazepam preparations, Cercine Injection and Cercine Tablet (Takeda Pharmaceutical Co. ) were used.
The potencies of diazepam effect varied according to the preparations and administration routes. 4.0-8.0 mg/kg of the injectable solution (Cercine Injection) given subcutaneously or intraperitoneally depressed the respondings in both CAR and DAR with a corresponding increase in the number of shock delivered. On the other hand, the same degree of this effect was obtained in the doses of 20.0-40.0 mg/kg of suspended solution of the tablet (Cercine Tablet) given orally.
Subcutaneous injection of 0.5-1.0 mg/kg selectively attenuated the conditioned suppression, but more than 2.0 mg/kg depressed even general responding. While 2.0 mg/kg of the tablet-suspension given orally was ineffective to attenuate the suppression, 10.0 mg/kg produced the same degree of the effect as 1.0 mg/kg given subcutaneously. Accordingly, when diazepam was administered subcutaneously or intraperitoneally, the effect was approximately 5-10 times potent independent of the schedules used, when compared with the oral administration.
The injectable preparation given orally showed the maximum effect much faster than the suspended solution of the tablet given in the same route, but the duration tended to be shorter.

View full abstract

Show abstractHide abstract

In order to confirm beneficial effects of L-Dopa on Parkinson's syndrome and to know an optimal dosage of the drug in Japanese, thirty-one patients with Parkinsonism were treated with L-Dopa. In thirteen cases of these patients, clinical evaluation was performed by use of cross-over double blind method. The optimal dose in Japanese ranged from 1 to 5.25 g. daily, with the average 3.39 g., which was considerably smaller than that used in U. S. A. or in Europe. In preliminary study, overall improvement was observed in 82.7% of patients, and L-Dopa was highly effective in every clinical feature which was evaluated, namely, rigidity, tremor and impairment in blinking, facial expression, speech, elevation of arms, gait and arm swing. Rate of improvement in tremor by the drug was almost same as that in rigidity. Significant improvement was observed in counting test, peg-board test, and steps and time required to walk ten meters.
Effects of L-Dopa on the following features were dose dependent: rigidity and tremor of upper extremities, arm swing, peg-board test, and steps and time required for walking ten meters. Cross-over double blind test revealed significant improvement in rigidity of both upper and lower extremities and arm swing as well as global judgement. Side effects encountered consisted of nausea, anorexia, vomiting, involuntary movements and visual hallucination. Nausea was the chief dose-limiting side effect, but involuntary movement was less frequent. It was concluded that L-Dopa appears to be effective for Parkinsonism with smaller dosage in Japanese than that in Occidentals.

View full abstract

Download PDF (1746K)

Register with J-STAGE for free!