levorphanol and Spasm

1. Naloxone was used to study the antagonism of the analgesic effects of some narcotics (morphine sulphate, levorphanol tartrate, and methadone hydrochloride) and narcotic antagonists (pentazocine, cyclazocine, and nalorphine hydrochloride). The analgesic assay used was the mouse phenylbenzoquinone stretching test.2. The in vivo equivalent of a pA(2) value (apparent pA(2)) for naloxone was determined with each agonist. These values were found to be significantly larger with the narcotics than with the narcotic antagonists.3. The slopes in the apparent pA(2) plots were also found to be significantly different. It was concluded that this difference in slopes was probably not due to a lack of equilibrium in one of the two groups of analgesics.4. The results suggest that the narcotic and the narcotic-antagonist analgesics may inhibit stretching in this assay by interacting either with two different receptors or with the same receptor in a different manner.

Topics: Animals; Bridged-Ring Compounds; Cyclazocine; Furans; Ketones; Levorphanol; Male; Methadone; Mice; Morphine; Nalorphine; Narcotic Antagonists; Pentazocine; Phenanthrenes; Quinones; Receptors, Drug; Spasm

1. Tolerance to the activity of several narcotic analgesics (morphine, levorphanol, and methadone) and several narcotic-antagonist analgesics (pentazocine, cyclazocine, and nalorphine) was studied in the mouse phenylbenzoquinone stretching test. Virtually complete tolerance was induced by chronic treatment with each of the narcotic agents, while no apparent tolerance was induced by the narcotic antagonists.2. In morphine-tolerant mice there was a high degree of cross-tolerance to the effects of not only the other narcotic drugs but also to those of the narcotic antagonists, acetylsalicylic acid, and physostigmine.3. The effects of morphine and pentazocine were antagonized by naloxone but not by atropine, while the effects of physostigmine were antagonized by atropine but not by naloxone. Neither atropine nor naloxone antagonized the effect of acetylsalicylic acid.4. The results of the tolerance study suggest that there is a fundamental difference in the consequences of receptor interaction for the narcotic and the narcotic-antagonist analgesics. Morphine-tolerant mice exhibit cross-tolerance non-specifically. The selectivity of naloxone and atropine differentiates the narcotic and narcotic-analgesics from the other two agents used in this analgesic test.

Topics: Analgesics; Animals; Aspirin; Atropine; Cyclazocine; Drug Tolerance; Levorphanol; Male; Methadone; Mice; Morphine; Nalorphine; Pentazocine; Physostigmine; Quinones; Receptors, Drug; Spasm