The Pharmacologic Effects of a New Analgesic α‐4‐Dimethylamino‐1,2‐Diphenyl‐3‐Methyl‐4‐Propionyloxybutane*
01 Aug 1955-Journal of the American Pharmaceutical Association (Elsevier)-Vol. 44, Iss: 8, pp 497-500
TL;DR: The results of pharmacologic studies with a new analgesic compound show analgesic activity in animals with a notable lack of tolerance development and/or respiratory depression.
Abstract: The results of pharmacologic studies with a new analgesic compound are presented. They show analgesic activity in animals with a notable lack of tolerance development and/or respiratory depression.
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01 Jan 1963
216 citations
TL;DR: A potent analgesic and a potent atropine-like substanc615, which sort of activity predominates seems to depend, in the first place, upon the nature of substituent R of structure 1.
Abstract: potent analgesic and a potent atropine-like substanc615. Which sort of activity predominates seems to depend, in the first place, upon the nature of substituent R of structure 1,. Analgesics have been found among compounds of the methadone type, for example I, R = COC,H,, methadols and acylated methadols, I, R = CHOR’C,H,; sulfones, I, R = SO,C,H,; esters, I, R = COOC,H, ; ketimines and acylated ketimines, I, R = C : NR’C,H,2p5*
173 citations
TL;DR: The delaying of transport of a charcoal meal paralleled depression of respiratory rate, and this is evidence for the participation of a central as well as a peripheral action in the effect of morphine on the gastrointestinal tract.
Abstract: In the rat, the ratio of the analgesic to the respiratory depressant potency was the same for morphine, codeine, diamorphine, methadone, dipipanone, piperidylisomethadone, phenadoxone, dextromoramide, and propoxyphene. The relative respiratory depressant activity of pethidine tended to be less, but the difference was not significant. The ratio of the analgesic dose to the dose preventing transport of a charcoal meal in the rat was about the same for morphine, codeine, pethidine, methadone, phenadoxone, dimethylthiambutene, and propoxyphene; the relative activities of these compounds in inhibiting the peristaltic reflex of the isolated guinea-pig ileum were also similar. However, because of differences in the slopes of regression lines in the charcoal meal test, some compounds (for example, morphine) had a greater effect on gastrointestinal propulsion than others (for example, pethidine) when given at moderate analgesic dose levels.In studies of the effects of intracisternal morphine in the rat, effects on the spinal reflex of the tail were to some extent dissociated from effects on the threshold for a squeak response. Further, the delaying of transport of a charcoal meal paralleled depression of respiratory rate, and this is evidence for the participation of a central as well as a peripheral action in the effect of morphine on the gastrointestinal tract. The delay in propulsion was reduced by nalorphine and increased by atropine and two general anaesthetic substances, but was unaffected by a number of other pharmacological agents.
87 citations
TL;DR: The human differs from the rat and dog in that propoxyphene metabolites are eliminated primarily in urine rather than bile, and the half-life of norpropoxymhene is also substantially longer than that of prop oxyphene.
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TL;DR: A quantitative method for measuring pain thresholds in the skin by thermal radiation has been described and pain sense was found to have no spatial summation in the sense that the pain threshold for many end organs was no lower than that for a few.
Abstract: The purpose of these studies has been to present a new method for measuring pain thresholds, together with experimental observations on the physiology of pain and on the effect of various chemical agents upon pain thresholds. Methods for estimating the intensity of the stimulus required to evoke a painful sensation in the skin may be classified under the headings: mechanical, chemical, electrical, and thermal. Conclusion 1. A quantitative method for measuring pain thresholds in the skin by thermal radiation has been described. The method has the general advantage of measuring a physical quantity which is directly proportional to the changes occurring in the skin. The method has the further advantages of precision, simplicity of technique, rapidity of measurement, and the fact that the stimulus is innocuous upon repeated application except at high intensities. Further, any part of the skin surface may be studied and the size of the stimulated area varied at will. 2. Pain thresholds measured in this way did not vary consistently with time of day, with the general effectiveness, or the emotional state of the 3 subjects. 3. Individual threshold measurements for 3 subjects were 0.229, 0.231, and 0.233 gm. cal./ sec./cm.2 and all measurements were found to be within + 12 per cent of their respective average values. The standard deviation for a single measurement was calculated to be + 2 per cent. 4. Intense pain in any part of the body raised the pain threshold in the skin in other parts as much as 35 per cent. 5. The senses of pain and heat, which were always stimulated together, were shown to be separate sensations through the action of acetylsalicylic acid. This drug lowered the heat threshold and raised the pain threshold. 6. The peripheral structures responsible tor pain sense were distinguished from those of temperature and touch by demonstrating that occluding the blood for 25 minutes did not directly affect the pain threshold in the ischemic hand, whereas other sensations could hardly be elicited. 7. Pain sense was found to have no spatial summation in the sense that the pain threshold for many end organs was no lower than that for a few. This was observed to be the case for minimal stimuli and for supraminimal stimuli after morphine administration. 8. The intensity of radiation which produced blistering in 3 seconds was observed to be twice that necessary for the bare perception of pain. PMID: 16694782 [PubMed] PMCID: PMC435000
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