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Chemical Compound Review

CHEMBL152023     N,N-diethyl-N'-(2- methoxyacridin-9...

Synonyms: AC1L8U1P, L001324
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Disease relevance of morphine


Psychiatry related information on morphine


High impact information on morphine


Chemical compound and disease context of morphine

  • 4 Morphine (5 x 10(-6) M) as well as the opioid peptides D-Ala2, N-Phe4, Met-(0)-01 (FK 33-824; 9 x 10(-7) M), D-Met2-Pro5 enkephalin (3 x 10(-7) M) and D-Ala2-D-Leu5-enkephalin (5 x 10(-6) M) inhibited the magnitude of the noncholinergic contracture but did not alter contractile responses to exogenous substance P (4 x 10(-11) M--4 x 10(-10) M) [16].
  • In diabetic rats, lacosamide attenuated cold (10, 30 mg/kg, i.p.), warm (3, 10, 30 mg/kg, i.p.) and mechanical allodynia (30 mg/kg, i.p.). Streptozotocin-induced thermal and mechanical hyperalgesia were reduced by lacosamide at doses of 10 and 30 mg/kg, i.p. Morphine (3 mg/kg) showed similar efficacy on allodynia and hyperalgesia [17].
  • BACKGROUND: A previous study showed a relation between pholcodine (PHO) consumption, prevalence of IgE-sensitization to PHO, morphine (MOR) and suxamethonium (SUX) and anaphylaxis to neuromuscular blocking agents (NMBA) [18].
  • 6 Morphine, enkephalins, opiate antagonists and cyclic guanosine 3',5'-monophosphate have a peripheral analgesic effect in the prostaglandin hyperalgesia test [19].
  • 3. To determine whether these effects were operative in the brain, rats received an injection of either morphine 50 micrograms/kg or its diluent (control) into the lateral cerebral ventricle intracerebroventricularly (i.c.v.). Morphine significantly increased (P < 0.05) the threshold for the development of arrhythmias [20].

Biological context of morphine


Anatomical context of morphine

  • DAMGO induced arrestin-2 translocation to the plasma membrane and considerable MOR1 internalization, whereas morphine did not induce arrestin-2 translocation and induced very little MOR1 internalization [25].
  • 2. Morphine (10(-8)-10(-7) M) markedly suppressed the amplitude of excitatory junction potential (e.j.p.) of ileum or that of vas deferens [21].
  • We show here that a glial modulator propentofylline (PPF) dramatically diminished the activation of astrocytes induced by drugs of abuse, such as methamphetamine (METH) and morphine (MRP) [26].
  • Acute treatments with high doses of sufentanil and morphine (mu-agonists), SNC-80 (delta-agonist), and U50488H (kappa-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine) [23].
  • Equipotent antinociceptive doses, as determined by a tail-flick response, for centrally administered (periaqueductal gray) morphine (M) and D-Ala2, D-Leu5 enkephalin (DADLE) were established as 5 micrograms and 19 micrograms, respectively [27].

Associations of morphine with other chemical compounds


Gene context of morphine

  • Culture supernatants were assayed by ELISA for CCL2 protein. beta-funaltrexamine (beta-FNA) was used to block mu-opioid receptor (MOR)s. RESULTS: Morphine upregulated CCL2 mRNA and protein in neuronal cultures in a concentration- and time-dependent fashion, but had no effect on CCL2 production in astrocyte or microglial cell cultures [30].
  • Both MOR and M6G increased the concentration of IGF binding protein-1 (IGFBP-1) in plasma and liver 2 h after injection [31].
  • We speculate that differential affinities of MOR and M6G to the different opiate receptor subtypes might be responsible for their distinct effects on GH/IGF-I system [31].
  • F9202, F9204, and Mor could significantly increase CREB phosphorylation from 2.88 to 3.59 folds over control levels after 30-min exposure [32].
  • CONCLUSION: Mor, F9202, and F9204, which could induce psychological dependence affected via the micro-opioid receptor, stimulated intracellular signal pathways involving Ca2+/calmodulin-dependent protein kinases (CCDPK) and protein kinase C (PKC) pathways, which in turn initiated CREB phosphorylation [32].

Analytical, diagnostic and therapeutic context of morphine

  • Chronic (28 day) subcutaneous infusion of clomipramine (CMI) via an Alzet minipump attenuated both central M-and DADLE-induced analgesia by day 15; attenuation persisted for the duration of the infusion (day 29) [27].
  • On the other hand, intra-nucleus accumbens (N.Acc.) administration of astrocyte-conditioned medium (ACM) aggravated the development of rewarding effects induced by METH and MRP via the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, which modulates astrogliosis and/or astrogliogenesis [26].
  • Sites of action of morphine involved in the development of physical dependence in rats. II. Morphine withdrawal precipitated by application of morphine antagonists into restricted parts of the ventricular system and by microinjection into various brain areas [33].
  • 4. Morphine (0.13-8 muM) inhibited the contractions of the cat nictitating membrane caused by electrical stimulation [34].
  • Dexketoprofen-induced antinociception in animal models of acute pain: Synergy with morphine and paracetamol [35].


  1. Effects of IV morphine in central pain: a randomized placebo-controlled study. Attal, N., Guirimand, F., Brasseur, L., Gaude, V., Chauvin, M., Bouhassira, D. Neurology (2002) [Pubmed]
  2. An opioid agonist that does not induce micro-opioid receptor--arrestin interactions or receptor internalization. Groer, C.E., Tidgewell, K., Moyer, R.A., Harding, W.W., Rothman, R.B., Prisinzano, T.E., Bohn, L.M. Mol. Pharmacol. (2007) [Pubmed]
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  4. Proceedings: Morphine hyperthermia, prostaglandin synthetase inhibitors and naloxone. Milton, A.S. J. Physiol. (Lond.) (1975) [Pubmed]
  5. Gallbladder nonvisualization with pericholecystic rim sign: morphine-augmentation optimizes diagnosis of acute cholecystitis. Oates, E., Selland, D.L., Chin, C.T., Achong, D.M. J. Nucl. Med. (1996) [Pubmed]
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  7. Genotype-dependent behavioral sensitivity to mu vs. kappa opiate agonists. I. Acute and chronic effects on mouse locomotor activity. Gwynn, G.J., Domino, E.F. J. Pharmacol. Exp. Ther. (1984) [Pubmed]
  8. Effects of opioid microinjections in the nucleus of the solitary tract on the sleep-wakefulness cycle states in cats. Reinoso-Barbero, F., de Andrés, I. Anesthesiology (1995) [Pubmed]
  9. NR2B-containing NMDA receptor is required for morphine-but not stress-induced reinstatement. Ma, Y.Y., Chu, N.N., Guo, C.Y., Han, J.S., Cui, C.L. Exp. Neurol. (2007) [Pubmed]
  10. Profiling the subjective, psychomotor, and physiological effects of a hydrocodone/acetaminophen product in recreational drug users. Zacny, J.P., Gutierrez, S., Bolbolan, S.A. Drug and alcohol dependence. (2005) [Pubmed]
  11. Death from heroin overdose: findings from hair analysis. Tagliaro, F., De Battisti, Z., Smith, F.P., Marigo, M. Lancet (1998) [Pubmed]
  12. Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation. Penagini, R., Bianchi, P.A. Gastroenterology (1997) [Pubmed]
  13. Comment on "Human White Blood Cells Synthesize Morphine: CYP2D6 Modulation". Boettcher, C., Fischer, W., Zenk, M.H. J. Immunol. (2006) [Pubmed]
  14. Involvement of dopamine system in regulation of Na+,K+-ATPase in the striatum upon activation of opioid receptors by morphine. Wu, Z.Q., Chen, J., Chi, Z.Q., Liu, J.G. Mol. Pharmacol. (2007) [Pubmed]
  15. Modulation of fear-potentiated startle and vocalizations in juvenile rhesus monkeys by morphine, diazepam, and buspirone. Winslow, J.T., Noble, P.L., Davis, M. Biol. Psychiatry (2007) [Pubmed]
  16. Effects of opioids on noncholinergic excitatory responses of the guinea-pig isolated ileum: inhibition of release of enteric substance P. Gintzler, A.R., Scalisi, J.A. Br. J. Pharmacol. (1982) [Pubmed]
  17. Antinociceptive efficacy of lacosamide in a rat model for painful diabetic neuropathy. Beyreuther, B., Callizot, N., Stöhr, T. Eur. J. Pharmacol. (2006) [Pubmed]
  18. Pholcodine stimulates a dramatic increase of IgE in IgE-sensitized individuals. A pilot study. Florvaag, E., Johansson, S.G., Oman, H., Harboe, T., Nopp, A. Allergy (2006) [Pubmed]
  19. Peripheral analgesia: mechanism of the analgesic action of aspirin-like drugs and opiate-antagonists. Ferreira, S.H. British journal of clinical pharmacology. (1980) [Pubmed]
  20. Morphine and morphiceptin increase the threshold for epinephrine-induced cardiac arrhythmias in the rat through brain mu opioid receptors. Rabkin, S.W. Clin. Exp. Pharmacol. Physiol. (1993) [Pubmed]
  21. Action of morphine on the neuro-effector transmission in the guinea-pig ileum and in the mouse vas deferens. Ito, Y., Tajima, K. J. Physiol. (Lond.) (1980) [Pubmed]
  22. Induction of SCE by opium pyrolysates in CHO cells and human peripheral blood lymphocytes. Perry, P.E., Thomson, E.J., Vijayalaxmi, n.u.l.l., Evans, H.J., Day, N.E., Bartsch, H. Carcinogenesis (1983) [Pubmed]
  23. Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: regulation by the ERK1/2 MAP kinase pathway. García-Fuster, M.J., Miralles, A., García-Sevilla, J.A. Neuropsychopharmacology (2007) [Pubmed]
  24. Opiate analgesics' dual role in firefly luciferase activity. Sudhaharan, T., Reddy, A.R. Biochemistry (1998) [Pubmed]
  25. Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells. Johnson, E.A., Oldfield, S., Braksator, E., Gonzalez-Cuello, A., Couch, D., Hall, K.J., Mundell, S.J., Bailey, C.P., Kelly, E., Henderson, G. Mol. Pharmacol. (2006) [Pubmed]
  26. Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse. Narita, M., Miyatake, M., Narita, M., Shibasaki, M., Shindo, K., Nakamura, A., Kuzumaki, N., Nagumo, Y., Suzuki, T. Neuropsychopharmacology (2006) [Pubmed]
  27. Effects of chronic clomipramine on central DADLE antinociception. Goldstein, F.J., Malseed, R.T., Nutz, J.F. Pain (1990) [Pubmed]
  28. Interactions between morphine and the opioid-like peptides in the rat vas deferens. Huidobro, F., Huidobro-Toro, J.P., Miranda, H. Br. J. Pharmacol. (1980) [Pubmed]
  29. The effect of l-stepholidine, a novel extract of Chinese herb, on the acquisition, expression, maintenance, and re-acquisition of morphine conditioned place preference in rats. Wang, W., Zhou, Y., Sun, J., Pan, L., Kang, L., Dai, Z., Yu, R., Jin, G., Ma, L. Neuropharmacology (2007) [Pubmed]
  30. Morphine stimulates CCL2 production by human neurons. Rock, R.B., Hu, S., Sheng, W.S., Peterson, P.K. Journal of neuroinflammation (2006) [Pubmed]
  31. Central opiate modulation of growth hormone and insulin-like growth factor-I. Hashiguchi, Y., Molina, P.E., Fan, J., Lang, C.H., Abumrad, N.N. Brain Res. Bull. (1996) [Pubmed]
  32. Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP- response element binding protein in cultured rat hippocampal neurons. Gao, C., Chen, L.W., Tao, Y.M., Chen, J., Xu, X.J., Chi, Z.Q. Acta Pharmacol. Sin. (2003) [Pubmed]
  33. Sites of action of morphine involved in the development of physical dependence in rats. II. Morphine withdrawal precipitated by application of morphine antagonists into restricted parts of the ventricular system and by microinjection into various brain areas. Laschka, E., Teschemacher, H., Mehraein, P., Herz, A. Psychopharmacologia. (1976) [Pubmed]
  34. The effects of morphine on the release of noradrenaline from the cat isolated nictitating membrane and the guinea-pig ileum myenteric plexus-longitudinal muscle preparation. Henderson, G., Hughes, J., Kosterlitz, H.W. Br. J. Pharmacol. (1975) [Pubmed]
  35. Dexketoprofen-induced antinociception in animal models of acute pain: Synergy with morphine and paracetamol. Miranda, H.F., Puig, M.M., Dursteler, C., Prieto, J.C., Pinardi, G. Neuropharmacology (2007) [Pubmed]
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