Some effects of levallorphan on responses to meperidine.

Patients with chronic pain of sufficient severity to require the use of narcotic analgesics served asthe subjects for the experiments. They were not told what drug' they were receiving or what was expected of them. All subjects were given saline, meperidine, and two ratios of meperidine and levaUorphan in successive trials; thus each patient served as his own control and as a basis for comparison. Effects on respiration were measured by testing the response of minute volume to the inhalation of 5 per cent carbon dioxide in oxygen. We believe this to lqe a more sensitive means of judging the reactivity of the respiratory centre than the measuring of respiratory minute volume while the subjects are breathing room air. Respiration was measured on a 18-htre Colhns resplrometer just before the injection of the drug, and 15, g0, 60, and 90 minutes thereafter "whenever this was practicable. The amount of analgesia was evaluated and recorded with the aid of a scale in which 0 indicated no pain; 1, slight pare; 2, moderate pain, and 3, severe pain. Each patient was questioned regardxng the character and degree of pain before and 15 and 80 minutes after the inlection and at 30-mmute intervals thereafter for a total of 4 hours. Accorchngly, dtfferences be[ween the pre-injection pain level and the respectave levels following the injection of the drug gave numbers which were used to inchoate the anaount of pare relief or "analgesia" for each time interval. Thus a difference of 0 meant no pain relief; 1, slight relief; 2, moderate relief, etc. These numbers were added for the entire period of the experiment to ymld a numerical expression of total pain relief. Observations of side reactions were also recorded. The patients were supine throughout the tame of observation. A period of at least 24 hours separated each experiment. All patien~:s were in pain (Grade 2 or 8) at the beginning of each trial. They were not Rermitted to receive a narcotic within 6 hours prior to any observataon period. The solution of meperidine (Demerol) hydrochloride contained 50 mg/ml . and that of levallorphan (Lorfan) 1 tartrate 1 mg./ml. Half of the patients received injections by the intramuscular route, and the other half by the subcutaneous route. The standard dose of meperidine was 100 mg. for four of the