A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice.

The addition of d-amphetamine to morphine has been reported to result in an increase of analgesic potency in experimental animals and man, but no data on the toxicity of such combinations are available. This study is intended to provide systematic information on the toxicity, analgesic potency and degree of physical impairment (swimming endurance) of a combination of 12 mg morphine sulfate with 10 mg d-amphetamine HCl per ml which is now under clinical investigation. Mice were used as experimental subjects. Meperidine, methadone and pentazocine were substituted for morphine using clinically equally analgesic doses and keeping the d-amphetamine amount constant. The toxicity of all analgesics especially that of morphine was enhanced in the combination, least so in the case of meperidine. The degree of increase of analgesic power by the addition of d-amphetamine was greatest with morphine and quantitatively in satisfactory agreement with present clinical experiences. However, the relationship between the increases of toxicity and of analgesia is not necessarily most favorable for this drug. For the other three analgesics increases in toxicity and analgesia were more in line, meperidine showing the best ratio. Swimming endurance was decreased with full analgesic doses of all four compounds. The presence of d-amphetamine tended to reverse this depression. The data were analyzed in relation to their possible predictive value for the use of such combinations in man for the therapeutic dose range and in the event of overdosage.