Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone (MET-CAMO) and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone (N-CPM-MET-CAMO) were tested in opioid receptor binding assays and in the mouse tail-flick test in order to characterize the affinity, selectivity and antinociceptive properties of these two compounds. Incubating bovine striatal membranes with either MET-CAMO or N-CPM-MET-CAMO produced a wash-resistant, concentration- and time-dependent inhibition of the binding of the mu-selective ligand, [3H]-[D-Ala2,MePhe4,Gly(ol)5]enkephalin, but with no change in delta or kappa binding. Preincubating membranes with N-CPM-MET-CAMO decreased the maximum binding value for [3H]-[D-Ala2,MePhe4,Gly(ol)5]enkephalin binding without changing the Kd value. In the mouse tail-flick assay, MET-CAMO and N-CPM-MET-CAMO did not produce any antinociception up to a dose of 100 nmol after i.c.v. administration. However, pretreatment of mice with either compound produced a time- and dose-dependent antagonism of morphine-induced antinociception. Analgesia mediated by delta or kappa opioids was not altered by either MET-CAMO or N-CPM-MET-CAMO at a dose of up to 100 nmol. The mu antagonistic effect of 1 nmol of MET-CAMO and N-CPM-MET-CAMO appeared at 8 hr and lasted up to 72 hr, with a maximal effect at 16 to 24 hr after i.c.v. administration. Pretreatment of mice with 1 nmol of MET-CAMO or N-CPM-MET-CAMO, given by i.c.v. administration at -24 hr, produced a rightward and downward shift of dose-response line of i.c.v. morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone: mu-selective irreversible opioid antagonists. 751 Nov 63

Irreversible opioid antagonists, when administered at small doses, require several hours to display their antagonism of antinociception mediated by opioid receptors. However, most opioid affinity ligands only need a few minutes to produce wash-resistant inhibition of opioid binding to brain membranes. Our study investigated whether the irreversible antagonists, beta-funaltrexamine (beta-FNA), 14 alpha, 14'beta-[dithiobis[(2-oxo-2,1-ethanediyl)imino]]-7,8-dihydro-N- (cyclopropylmethyl)normorphine (N-CPM-TAMO), and N-cyclopropylmethyl-5 beta-methyl- beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone (N-CPM-MET-CAMO) had any effect on morphine-induced antinociceptive tolerance before the appearance of their antagonism in the mouse tail-flick assay. All opioids were given by i.c.v. administration. The irreversible antagonists, beta-FNA (20 nmol), N-CPM-TAMO (0.5 nmol) and N-CPM-MET-CAMO (1 nmol) did not produce any antagonism of morphine-induced analgesia until at least 8 hr after administration. Pretreatment with morphine (3 nmol, -140 min) produced acute antinociceptive tolerance as demonstrated by a 45-fold rightward shift of the morphine dose-response curve. When coadministered with morphine, beta-FNA, N-CPM-TAMO and N-CPM-MET-CAMO completely prevented the development of morphine tolerance 140 min after administration in a dose-dependent manner. This preventive effect lasted for up to 420 min, during which time, morphine was given repeatedly up to four times. This antinociception produced by morphine after coadministration with irreversible antagonists was antagonized by naloxone, demonstrating that morphine-induced analgesia was still mediated by opioid receptors. The kappa- and delta-selective opioid antagonists, nor-binaltorphimine and ICI 174,864, respectively, did not block the preventive effect produced by the irreversible antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preventing morphine antinociceptive tolerance by irreversible mu opioid antagonists before the onset of their antagonism. 775 70

The affinity, selectivity and antinociceptive properties of 5 beta-methyl-14 beta-(p-chlorocinnamoylamino)-7,8-dihydromorphinone (MET-Cl-CAMO) and N-cyclopropyl-methyl-5 beta-methyl-14 beta-(p-chlorocinnamoylamino)-7, 8-dihydronormorphinone (N-CPM-MET-Cl-CAMO) for the multiple opioid receptors were characterized. In competition binding assays using bovine striatal membranes, both compounds inhibited the binding of 0.25 nM [3H][D-Ala2, (Me)-Phe4,Gly(ol)5]enkephalin (DAMGO) with IC 50 values of less than 2 nM. Preincubation of membranes with MET-CI-CAMO and N-CPM-MET-Cl-CAMO produced a concentration-dependent, wash-resistant inhibition of mu-opioid receptor binding. Saturation binding experiments with N-CPM-MET-Cl-CAMO showed a reduction in the number of mu-opioid binding sites without a change in affinity. In the mouse 55 degrees C warm-water tail-flick assay, neither MET-Cl-CAMO nor N-CPM-MET-Cl-CAMO at doses up to 100 nmol produced antinociception after intracerebroventricular administration, but morphine-induced antinociception was antagonized in a time- and dose-dependent manner by both compounds. The antagonism produced by 1 nmol of either MET-Cl-CAMO or N-CPM-MET-Cl-CAMO reached a maximal effect after 24 h, and lasted up to 48 h. Analgesia mediated by delta- or kappa-opioids was not altered by either compound. In summary, the data suggest that MET-Cl-CAMO and N-CPM-MET-Cl-CAMO are long-term, mu-opioid receptor antagonists, devoid of agonist properties in the mouse tail-flick assay, and that N-CPM-MET-Cl-CAMO may produce its antagonistic effects by binding irreversibly to the mu-opioid receptor.
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PMID:14 beta-Chlorocinnamoylamino derivatives of metopon: long-term mu-opioid receptor antagonists. 905 44

Male piglets are castrated to reduce boar taint and also to reduce aggressive and sexual behaviour. However, the procedure as traditionally performed is painful and negatively affects performance. Large-scale results about the consequences of implementing alternatives on farms are lacking. We, therefore, investigated the practical applicability of the following five alternatives that can be implemented in the short term: surgical castration (1) without pain relief (CONT, control group), (2) with analgesia (MET, Metacam, 0.2 ml, 10 to 15 min before castration), (3) with general anaesthesia (CO2, inhalation, 100% CO2, 25 s, 3 l/min), (4) vaccination against boar taint (IM, two injections with Improvac) and (5) production of entire males (EM). The study consisted of the following two trials: (1) an experimental farm trial with 18 animals/treatment and (2) a large field trial on 20 farms with ~120 male pigs/farm per treatment and all treatments performed on each farm. Performance results as well as data on carcass traits, boar taint (hot-iron method) and testes development and weight were collected in both trials. Neither castration nor administration of analgesia or anaesthesia had an effect on daily gain of the piglets in the farrowing crates (P>0.05). Farmer records indicated that mortality in the farrowing crates (1.1%), nursery pens (1.8%) and fattening stable (2.2%) was not influenced by MET or CO2 compared with EM, IM or CONT (P>0.05). No significant differences were found for daily gain (P>0.05) nor slaughter age (P>0.05). Immunocastrates and EM had a better gain-to-feed ratio (P<0.05) compared with the groups of barrows (CONT, MET and CO2). Lean meat percentage was higher for EM compared with the barrows, and intermediate for IM (P<0.05). Carcass yield was lowest for IM (P<0.05). The hot-iron method indicated that boar taint was eliminated in barrows and IM compared with EM (P<0.001). Average prevalence of strong boar taint was 3% for EM, but varied from 0% to 14% between farms. As the effect of treatment on performance as well as the level of boar taint of EM was farm dependent, farmers should be encouraged to pre-test the different alternatives in order to make a well-considered choice for the best practical and profitable alternative for their farm.
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PMID:Field experience with surgical castration with anaesthesia, analgesia, immunocastration and production of entire male pigs: performance, carcass traits and boar taint prevalence. 2543 16