Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure.

The analgesic activity of morphine and the narcotic antagonists, pentazocine, cyclazocine, levallorphan and nalorphine, was assessed in the rat using two hot plates: one maintained at 49.5 degrees C and the other at the "standard" 54.5 degrees C. The analgesic effects of morphine using the 49.5 degrees C hot plate were of a significantly greater magnitude than its effects using the 54.5 degrees C hot plate for both nontolerant and morphine-tolerant subjects. Dose-related effects were observed with all of the narcotic antagonists tested using the 49.5 degrees C hot plate; only the highest dose of pentazocine exhibited activity using the 54.5 degrees C hot plate. Naloxone (3.0 mg/kg) antagonized the analgesic effects of morphine and all of the narcotic antagonists, but was without activity itself when tested using the 49.5 degrees C hot plate at doses as high as 30 mg/kg. Aspirin was also inactive using the 49.5 degrees C plate, whereas physostigmine increased latencies only at a dose that produced severe motor deficit. A low temperature hot plate is recommended for evaluating the analgesic activity of narcotic antagonists in the rat. This simple procedure provides results which are dose-related, quantifiable, reproducible, of a large magnitude and specific.