THE EVALUATION OF THE ANALGESIC ACTION OF METHADON ISOMERS AND OTHER ANALGESICS BY A NEW RAPID SCREENING METHOD

¹ Maltbie Chemical Co., Morristown, N. J.

1. A simple and accurate method is described by which analgesics may be rapidly screened. It has been applied to morphine, codeine, merperidine, methadon isomers, ketobemidone, aminopyrine, and acetylsalicylic acid.

2. This method is based on an all-or-none response towards a pain heat stimulus of constant intensity and duration. A linear relationship exists between the logarithm of the doses of analgesic and the probit of rats failing to respond to the pain stimulus.

3. Statistical analysis of the data shows that the method has satisfactory inherent precision and yields reproducible results which are in agreement with clinical experience.

4. Evaluated by this method the two opiates tested and merperidine have the following average effective dose after subcutaneous administration expressed in mgm./kgm. of rat: morphine, 3.01; codeine, 24; merpenidine, 21. The peak of action is thirty minutes. Using the average effective dose, the duration of analgesic activity of merperidine is two and one-half hours, and of morphine and codeine, three and one-half hours.

5. Methadon, its isomers, and ketobemidone show the following E.D. 50: dl-Methadon(B) 2.5mgm./kgm., dl-Methadon (W) 2.3 mgm./kgm., d-Methadon 82 mgm./kgm., 1-Methadon 1.05 mgm./kgm., 1-Isomethadon 3.5 mgm./kgm., and ketobemidone 2.9 mgm./kgm. The duration of analgesic activity is more than two and one-half hours except for d-Methadon where it is less than two hours.

6. Among minor analgesics, aminopyrine is active only when the flight reaction is used as the end point. No linear dose-effect relationship can be observed. Acetylsalicylic acid given orally or intraperitoneally is inactive by this method. If a smaller intensity of heat is used as painful stimulus, however, a slight but definite "analgesia" is observed.