nalorphine and Spasm

Topics: Age Factors; Analgesics; Animals; Aspirin; Behavior, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electrodes, Implanted; Electroshock; Hot Temperature; Methods; Mice; Nalorphine; Narcotic Antagonists; Narcotics; Pain; Pressure; Rats; Reaction Time; Reflex; Sex Factors; Spasm; Species Specificity; Tail; Time Factors; Vocalization, Animal

A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists.

Topics: Acetylcholine; Analgesics, Opioid; Animals; Azocines; Mice; Molecular Conformation; Narcotic Antagonists; Phenazocine; Rats; Spasm; Structure-Activity Relationship; Thebaine

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

1. The antinociceptive activity of morphine, nalorphine, oxotremorine and eserine has been examined in mice in electroshock and phenylbenzoquinone writhing tests.2. The effectiveness of these drugs alone, in combination with each other, and in combination with the muscarinic antagonist atropine sulphate, and with the narcotic antagonist naloxone has also been investigated.3. In both tests morphine was effective and antagonized by naloxone.4. Nalorphine was active in the phenylbenzoquinone test but only slightly active in the electroshock test: it was antagonized by naloxone in both tests.5. Morphine was potentiated by nalorphine in the phenylbenzoquinone test. but antagonized by it in the electroshock test.6. Oxotremorine was effective in both tests, and was antagonized by atropine sulphate.7. Eserine was active only in the phenylbenzoquinone test, and was antagonized by atropine sulphate.8. Oxotremorine was potentiated by eserine in the phenylbenzoquinone test, but antagonized by it in the electroshock test.9. Crossed agonist and partial agonist experiments produced enhancement.10. No antagonism was seen in the crossed antagonist experiments.11. The similarities between the effects of the two classes of drugs are discussed, and the conclusion drawn that they act by separate mechanisms.

Topics: Analgesia; Animals; Atropine; Bridged-Ring Compounds; Drug Synergism; Electroshock; Furans; Ketones; Mice; Morphine; Nalorphine; Phenanthrenes; Physostigmine; Pyrrolidinones; Quinones; Sensory Receptor Cells; Spasm

Topics: Aminopyrine; Animals; Anti-Inflammatory Agents; Arachidonic Acids; Codeine; Furans; Glycosides; Injections, Intraperitoneal; Male; Mice; Morphine; Nalorphine; Pentazocine; Phenacetin; Phenylbutazone; Sodium Salicylate; Spasm

Topics: Analysis of Variance; Animals; Depression, Chemical; Male; Mice; Morphine; Muscles; Nalorphine; Pain; Quinones; Spasm; Time Factors

Topics: Analgesics; Humans; Intestines; Nalorphine; Spasm