Effect of narcotics on enzymes of acetylcholine metabolism in cultured cells from embryonic chick brains.
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Time effects of three doses of codeine, d-propoxyphene, meperidine and dextromethorphan upon locomotor activity have been investigated in naive rats as well as in animals treated chronically with 20 mg/kg of morphine daily. The first three drugs exhibited a motility pattern qualitatively similar to that of morphine; in chronically-treated rats cross-tolerance occurred to acute depressant effects and cross-sensitization to acute excitatory effects. In the case of meperidine however cross-sensitization appeared to be small. Dextromethorphan presented effects similar to morphine only in a very large dose. The present data, together with those of previous work, demonstrate that a locomotor activity substitution test may predict the morphine-like addictive properties of a drug.
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QSAR estimates of toxicity of relatively unreactive organic chemicals for 19 species of bacteria, algae, fungi, protozoans, coelenterates, rotifers, molluscs, crustaceans, insects, fish and amphibians were used to predict 'no-effect-levels' (NELs) at the ecosystem level by means of a recently developed extrapolation model. Equilibrium-partitioning theory for sediment and water was used to derive NELs for aquatic sediments. A simple table is given from which NELs for water and sediments can be predicted on the basis of only the octanol-water partition coefficient and molecular weight.
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Guinea pigs were injected SC for 3 weeks with 3 different dosage schedules of morphine or methadone, or with saline. For 8 weeks thereafter they were challenged weekly with the dopamine agonist apomorphine. Hypersensitivity was manifested in more intense stereotypies, as compared to the saline group, by all morphine and methadone groups. Hypersensitivity persisted longer after the termination of methadone treatment (maximum of 8 weeks) than after morphine administration (maximum of 3 weeks). The degree of hypersensitivity, and its duration after treatment, was positively related to methadone dosage. In some groups a period of hyposensitivity was seen following hypersensitivity. These data are interpreted with reference to the hypothesized mechanism underlying the development of hypersensitivity, the different durations of action of morphine and methadone, and the retention of methadone in brain following treatment.
The present study examined the effect of opiate antagonists on clonidine-induced feeding in rabbits. The change in food intake induced by clonidine was blocked by naltrexone. The active (-)-isomer of the antagonist 5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan had an effect similar to naltrexone. Similar doses of the (+)-isomer were inactive, except at the highest dose used in the study. The results suggest that opiate antagonists block feeding elicited by a specific noradrenoreceptor agonist and that this inhibition is due to a direct interaction with opiate systems.
We have studied the kinetics of the conservative behavior of systems which are subject to the dual action of an external effector or a negative feedback. Conditions have been found under which the dual-action mechanism produces conservative behavior. Negative feedback alone was shown not to produce the conservative behavior of an enzyme-receptor system.
Physicians have been frequently reported to prescribe inadequately pain medication in the hospitalized patient. A number of methods and techniques have been attempted to alter this phenomenon including audit, standard setting, drug utilization evaluation and sanctioning. The purpose of the following study was to demonstrate the behavioral efficacy of the technique of detailing. We reviewed the postsurgical records of 320 patients for pre-established criteria on the administration of meperidine before and after detailing of the proper prescribing with regard to timing and dose. The data show 30% of the sample meeting the criteria before detailing and 43% after detailing had been given. We conclude the method of detailing can be effective in altering physician's prescribing behavior for meperidine in postoperative surgical patients.
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Recent data reveal that only a small number of opioid addicts who attempt to detoxify from methadone maintenance programs will be successful. An irrational fear of detoxification has been postulated to be one reason for detoxification not being more efficacious. The present investigation attempted to assess both self-report and psychophysiological responses to detoxification and neutral scenes in two groups of persons on methadone maintenance. The two groups (N = 8 each) were selected by two blind interviewers as either having or not having a detoxification fear. After imagery training, subjects were asked to imagine 10 scenes, alternating between neutral and detoxification scenes with random counterbalancing for order, while the psychophysiological dependent measures and self-report anxiety and clarity ratings were assessed. Some of the self-report and psychophysiological measures were significantly different for scene type, indicating a successful manipulation of scene imagery. Further, pulse volume measures indicated greater activation in the fear group than in the non-fear group to the detoxification scenes. The results are discussed in terms of providing evidence for greater activation, presumably due to greater anxiety, for the detoxification fear subjects than the non-fear subjects specific to the detoxification imagery and in terms of potential treatment implications.