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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of the stereoisomers of the centrally acting analgesic 1-[1-(2-chlorobenzyl)-pyrrol-2-yl]-2-di-sec.-butylamino-ethanol (viminol) is described. Their absolute configuration has been shown by comparing the circular dichroism (CD) curves with those of some phenyl analogs: for one of the viminol stereoisomers the postulated configurational assignment has been recently confirmed by an X-ray analysis. The pharmacological properties shared by the viminol stereoisomers are also described. The R,R configuration of the sec.-butyl groups and the S configuration of the hydroxy group appear to be essential for the agonistic effects: analgesia, tolerance and physical dependence in rodents. The S,R,R configurated viminol does not substitute, however, for morphine in monkeys, using the single dose suppression test. S,S or R,S(S,R) configurations of the sec.-butyl groups are associated with antagonistic properties. The binding capacity of the viminol stereoisomers to the opiate receptors and their influence on the acetylcholine release from the intestinal cholinergic terminals electrically stimulated are also described.
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PMID:Stereochemistry of viminol, a novel central analgesic. 3 16

Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties. In rodent antiwrithing analgesic tests, butorphanol was 4 to 30 times more potent than morphine and dl-pentazocine, respectively. As an antagonist, butorphanol was about equivalent to nalorphine and 30 times more potent than dl-pentazocine. On the basis of the naloxone-induced mouse jumping test and the lack of substitution in withdrawn morphine-dependent mice, it is estimated that the potential for physical dependence of butorphanol will be less than that of dl-pentazocine but greater than that of nalorphine and dl-cyclazocine. Animal data also show that agonistic actions of butorphanol, such as respiratory depression and miosis, reach ceiling effects which are lower than those seen with morphine with an increase in dosage. Thus, butorphanol differed from morphine which exhibited agonist effects in a dose-related manner. Butorphanol showed weak to moderate central depressant properties at doses which were considerably higher (greater than 100 X) than those producing analgesia. Minimal cardiovascular and respiratory effects were seen with butorphanol in conscious dogs.
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PMID:The pharmacology of butorphanol, a 3,14-dihydroxymorphinan narcotic antagonist analgesic. 6 89

Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.
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PMID:Naloxone. 18 95

A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.
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PMID:Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines. 20 68

The peptide-Z-Pro-D-Leu, injected daily in mice receiving morphine chronically, was found to prevent development of physical dependence as measured by changes in body temperature and body weight due either to abrupt or to naloxone-induced withdrawal. On the other hand, administration of Z-Pro-D-Leu only on the last day of morphine treatment did not alter the overt signs of withdrawal. Daily administration of Z-Pro-D-Leu was also effective in blocking the development of tolerance to the analgesic and the hypothermic effects of subsequent challenge doses of morphine. However, the peptide treatment did not alter the acute effects of a challenge dose of morphine on either analgesia or body temperature. No effects on memory were noted, as evaluated in a one-trial passive avoidance task. Clinical implications of the use of Z-Pro-D-Leu are discussed.
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PMID:Inhibition by Z-Pro-D-Leu of development of tolerance to and physical dependence on morphine in mice. 27 36

The effect of morphine on the uptake of 45Ca++ was studied in lysed synaptosomes obtained from homogenates of whole mouse brain. The addition of morphine, 10(-6) M, to the incubation medium or acute administration of 10 or 20 mg/kg s.c. resulted in a decrease in 45Ca++ uptake; this decrease was observed only in the presence of ATP (3 mM). In contrast, after morphine pellet implantation (72 hr) to induce tolerance and physical dependence, an enhancement of lysed synaptosomal 45Ca++ uptake occurred; the increase was obtained in the presence but not in the absence of ATP. The enhancement of Ca++ uptake appears to be related with the degree of tolerance and dependence development since a linear relationship was noted between the time of morphine pellet implantation and the increase in 45Ca++ uptake by lysed synaptosomes. The acute inhibitory action on 45Ca++ uptake by morphine was prevented in vitro by naloxone, 1.9 x 10(-8) M, and in vivo by 2 mg/kg of naloxone s.c. and the chronic enhancing action of morphine by the simultaneous implantation of a naloxone pellet with the morphine pellet. The present findings lend further support to our previous reports in which we suggest that alterations in Ca++ flux may be involved with morphine analgesia, tolerance and physical dependence.
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PMID:Effect of morphine on calcium uptake by lysed synaptosomes. 50 67

1. Tolerance to morphine-induced analgesia (hot plate and acetic acid whrithing test), hypothermia and lethality can be quantified in mice by measuring the degree of parallel shifts of semilog. dose-response relationships induced by repeated opioid administration. 2. A similar procedure can be used for the quantification of naloxone-induced withdrawal as an indicator of dependence. 3. The intensity of tolerance development with respect to time of administration and dosage of morphine varies with the test procedure. It is closely parallel, however, in both analgesic tests during acquisition of tolerance. 4. Log-log-linear relationships exist between tolerance in analgesic tests and physical dependence as determined by naloxone-induced withdrawal. 5. The minimum tolerance-inducing dose of morphine in different tests could not be correlated to the ED50's in these tests. 6. Chronic opiate treatment leads to a decrease or an increase in motility response to morphine, depending on the time that has elapsed after the last morphine administration.
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PMID:Quantitative assessment of tolerance to and dependence on morphine in mice. 55 28

Tolerance to and physical dependence on morphine in the rat was induced by injecting increasing doses of morphine sulfate (M.S.) administered i.p. twice daily for 14 days. The last dose of M.S. was 200 mg/kg. This procedure produced a 4-fold tolerance to morphine as evidence by the increased dose of morphine required to produce analgesia. The degree of dependence was quantified by determining the naloxone ED50 for the stereotyped withdrawal jumping response. Body weight loss and hypothermic responses during abrupt and naloxone-induced withdrawal were also measured. The degree of tolerance and dependence produced by multiple injection procedure was comparable to that produced by 2 pellets containing 75 mg of morphine base implanted for 3 days. The level and turnover of brain serotonin, determined 6 or 12 h after the last morphine sulfate injection did not differ significantly from that of saline injected control animals. These data indicate that multiple injection technique produces a mild degree of tolerance to, and physical dependence on, morphine which was not related to changes in brain serotonin level or turnover.
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PMID:Brain serotonin turnover and morphine tolerance-dependence induced by multiple injections in the rat. 56 Mar 5

The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence.
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PMID:Effect of morphine on synaptosomal Ca++ uptake. 57 Oct 16

The effects of single and repeated pargyline administration on morphine antinociception in both naive and morphine-tolerant mice and on naloxone-precipitated withdrawal in morphine tolerant-dependent animals were investigated. Adult, male Swiss-Webster mice were rendered tolerant to and dependent on morphine by the s.c. pellet implantion technique. Morphine analgesia, as assessed by the tail-flick antinociceptive test, was potentiated in tolerant animals by acute adminstration of pargyline but antagonized by repeated pargyline administration; pargyline produced similar effects in non-tolerant mice and to the same relative degree. Repeated pargyline treatment during morphine pellet implantation enhanced the withdrawal jumping response precipitated by naloxone in dependent mice. Pargyline also, after a single injection, exacerbated jumping in mice undergoing abrupt withdrawal. Neither acute nor chronic pargyline administration altered the brain distribution of injected morphine in non-tolerant mice. It was concluded that pargyline may modify acute morphine actions and withdrawal without materially altering the process(es) involved in the development of tolerance and physical dependence.
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PMID:Effect of pargyline on morphine tolerance and physical dependence development in mice. 98 7


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