morphinans

Summary

Summary: Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.

Top Publications

  1. Wang M, Chang C, Cheng J, Wu H, Li Y, Cheng J. Activation of opioid mu-receptor by sinomenine in cell and mice. Neurosci Lett. 2008;443:209-12 pubmed publisher
    ..Long-term pretreatment with sinomenine may delay the analgesic tolerance of morphine. The obtained results suggest that sinomenine has an ability to activate OMR, implicating the potential of sinomenine to be applied in clinic. ..
  2. Inan S, Dun N, Cowan A. Nalfurafine prevents 5'-guanidinonaltrindole- and compound 48/80-induced spinal c-fos expression and attenuates 5'-guanidinonaltrindole-elicited scratching behavior in mice. Neuroscience. 2009;163:23-33 pubmed publisher
    ..On the basis of our results, nalfurafine holds promise as a potentially useful antipruritic in human conditions involving itch. ..
  3. Chan K, Liu Z, Jiang Z, Zhou H, Wong Y, Xu H, et al. The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. J Ethnopharmacol. 2006;103:425-32 pubmed
    ..The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein...
  4. Shin E, Hong J, Kim H. Neuropsychopharmacological understanding for therapeutic application of morphinans. Arch Pharm Res. 2010;33:1575-87 pubmed publisher
    b>Morphinans are a class of compounds containing the basic structure of morphine. It is well-known that morphinans possess diverse pharmacological effects on the central nervous system...
  5. Schütz J, Spetea M, Koch M, Aceto M, Harris L, Coop A, et al. Synthesis and biological evaluation of 14-alkoxymorphinans. 20. 14-phenylpropoxymetopon: an extremely powerful analgesic. J Med Chem. 2003;46:4182-7 pubmed
    ..twice as potent in the tail-flick assay than this reference compound. The 3-O-alkyl ethers of PPOM, compounds 6 and 8, showed less potency in in vivo assays, but partly surpassed the potency of the 3-OH analogue 14-methoxymetopon (1). ..
  6. Wu W, Wu P, Chen X, ZHANG Z, Gu J, Yang Y, et al. Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid-sensing ion channel 1a and L-type calcium channels. Br J Pharmacol. 2011;164:1445-59 pubmed publisher
    ..The inhibitory effects of SN on acid-sensing ion channel 1a and L-type calcium channels are involved in this neuroprotection. ..
  7. Mark W, Schneeberger S, Seiler R, Stroka D, Amberger A, Offner F, et al. Sinomenine blocks tissue remodeling in a rat model of chronic cardiac allograft rejection. Transplantation. 2003;75:940-5 pubmed
  8. Moore K, Ramcharitar V, Levine B, Fowler D. Tentative identification of novel oxycodone metabolites in human urine. J Anal Toxicol. 2003;27:346-52 pubmed
  9. Cheng Y, Zhang J, Hou W, Wang D, Li F, Zhang Y, et al. Immunoregulatory effects of sinomenine on the T-bet/GATA-3 ratio and Th1/Th2 cytokine balance in the treatment of mesangial proliferative nephritis. Int Immunopharmacol. 2009;9:894-9 pubmed publisher
    ..These results suggest that a shift toward the Th1 pathway of Th cell activation occurs in MsPGN patients, and that sinomenine has the potential to counter this shift in the Th1/Th2 balance and thereby produce therapeutic effects. ..

More Information

Publications62

  1. Wang Y, Tao Y, Li F, Wang Y, Xu X, Chen J, et al. Pharmacological characterization of ATPM [(-)-3-aminothiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride], a novel mixed kappa-agonist and mu-agonist/-antagonist that attenuates morphine antinociceptive tolerance and heroin self-administration. J Pharmacol Exp Ther. 2009;329:306-13 pubmed publisher
    ..kappa-Agonists with some mu-activity appear to offer some advantages over selective kappa-agonists for the treatment of heroin abuse. ..
  2. Kawai K, Hayakawa J, Miyamoto T, Imamura Y, Yamane S, Wakita H, et al. Design, synthesis, and structure-activity relationship of novel opioid kappa-agonists. Bioorg Med Chem. 2008;16:9188-201 pubmed publisher
    ..Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described. ..
  3. Lattanzi R, Spetea M, Schüllner F, Rief S, Krassnig R, Negri L, et al. Synthesis and biological evaluation of 14-alkoxymorphinans. 22.(1) Influence of the 14-alkoxy group and the substitution in position 5 in 14-alkoxymorphinan-6-ones on in vitro and in vivo activities. J Med Chem. 2005;48:3372-8 pubmed
    ..further evidence that the nature of the substituent at position 14 has a major impact on the abilities of morphinans to interact with opioid receptors...
  4. Kummer O, Hammann F, Moser C, Schaller O, Drewe J, Krahenbuhl S. Effect of the inhibition of CYP3A4 or CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Eur J Clin Pharmacol. 2011;67:63-71 pubmed publisher
    ..Pharmacodynamic changes associated with CYP3A4 inhibition may be clinically important in patients treated with oxycodone. ..
  5. Greiner E, Spetea M, Krassnig R, Schüllner F, Aceto M, Harris L, et al. Synthesis and biological evaluation of 14-alkoxymorphinans. 18. N-substituted 14-phenylpropyloxymorphinan-6-ones with unanticipated agonist properties: extending the scope of common structure-activity relationships. J Med Chem. 2003;46:1758-63 pubmed
    ..09 nm). ..
  6. Saari T, Grönlund J, Hagelberg N, Neuvonen M, Laine K, Neuvonen P, et al. Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone. Eur J Clin Pharmacol. 2010;66:387-97 pubmed publisher
    ..The clinical use of itraconazole in patients receiving multiple doses of oxycodone for pain relief may increase the risk of opioid-associated adverse effects. ..
  7. Zhou H, Wong Y, Wang J, Cai X, Liu L. Sinomenine ameliorates arthritis via MMPs, TIMPs, and cytokines in rats. Biochem Biophys Res Commun. 2008;376:352-7 pubmed publisher
  8. Spetea M, Greiner E, Aceto M, Harris L, Coop A, Schmidhammer H. Effect of a 6-cyano substituent in 14-oxygenated N-methylmorphinans on opioid receptor binding and antinociceptive potency. J Med Chem. 2005;48:5052-5 pubmed
    In a continued effort to find new substitution patterns in morphinans that would produce strong antinociception while inducing lesser side effects, 4,5-oxygen bridge-opened 6-cyano-substituted N-methylmorphinans (1-3) were synthesized...
  9. Wu H, Wacker D, Mileni M, KATRITCH V, Han G, Vardy E, et al. Structure of the human ?-opioid receptor in complex with JDTic. Nature. 2012;485:327-32 pubmed publisher
  10. Qian L, Xu Z, Zhang W, Wilson B, Hong J, Flood P. Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase. J Neuroinflammation. 2007;4:23 pubmed
    ..These findings suggest a novel therapy to treat inflammation-mediated neurodegenerative diseases. ..
  11. Spetea M, Schüllner F, Moisa R, Berzetei Gurske I, Schraml B, Dörfler C, et al. Synthesis and biological evaluation of 14-alkoxymorphinans. 21. Novel 4-alkoxy and 14-phenylpropoxy derivatives of the mu opioid receptor antagonist cyprodime. J Med Chem. 2004;47:3242-7 pubmed
    ..further evidence that the nature of the substituent at position 14 has a major impact on the abilities of morphinans to interact with opioid receptors...
  12. Wang W, Wang P, Li X. [The effect of sinomenine on cyclooxygenase activity and the expression of COX-1 and COX-2 mRNA in human peripheral monocytes]. Zhongguo Zhong Yao Za Zhi. 2003;28:352-5 pubmed
    ..To observe in vitro the effect of Sinomenine, a pure alkaloid extracted from the chinese medical plant Sinomenium acutum on the activity of cyclooxygenase (COX-1 and COX-2) and the expression of COX-1 and COX-2 mRNA...
  13. Naito T, Takashina Y, Yamamoto K, Tashiro M, Ohnishi K, Kagawa Y, et al. CYP3A5*3 affects plasma disposition of noroxycodone and dose escalation in cancer patients receiving oxycodone. J Clin Pharmacol. 2011;51:1529-38 pubmed publisher
    ..In conclusion, CYP3A5*3 altered the plasma disposition of noroxycodone, which was inversely affecting the dose escalation in cancer patients receiving oxycodone. ..
  14. Al Khrasani M, Spetea M, Friedmann T, Riba P, Kiraly K, Schmidhammer H, et al. DAMGO and 6beta-glycine substituted 14-O-methyloxymorphone but not morphine show peripheral, preemptive antinociception after systemic administration in a mouse visceral pain model and high intrinsic efficacy in the isolated rat vas deferens. Brain Res Bull. 2007;74:369-75 pubmed
    ..Our findings support the role of peripheral MOR in the pathology of pain states involving sensitization of peripheral nociceptors...
  15. Huang F, Yamaki K, Tong X, Fu L, Zhang R, Cai Y, et al. Inhibition of the antigen-induced activation of RBL-2H3 cells by sinomenine. Int Immunopharmacol. 2008;8:502-7 pubmed publisher
    ..These results suggested that SIN might suppress the antigen-induced activation of RBL-2H3 cells via a Ca2+ independent pathway. ..
  16. Qi C, Zou H, Zhang C, Xie Q, Jin M, Yu L. Effect of GNTI, a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice. Acta Pharmacol Sin. 2006;27:1401-8 pubmed
    ..GNTI appears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo. ..
  17. Song S, Shen X, Tang Y, Wang Z, Guo W, Ding G, et al. Sinomenine pretreatment attenuates cold ischemia/reperfusion injury in rats: the role of heme oxygenase-1. Int Immunopharmacol. 2010;10:679-84 pubmed publisher
    ..Thus, SIN deserves further exploration as a novel agent to attenuate I/R injury. ..
  18. Kok T, Yue P, Mak N, Fan T, Liu L, Wong R. The anti-angiogenic effect of sinomenine. Angiogenesis. 2005;8:3-12 pubmed
    ..Therefore, the inhibition of leukocytes migration across blood vessel walls and the anti-angiogenic effect of sinomenine may contribute towards its therapeutic mechanisms in alleviating the pathogenesis of RA. ..
  19. Schuster D, Spetea M, Music M, Rief S, Fink M, Kirchmair J, et al. Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors. Bioorg Med Chem. 2010;18:5071-80 pubmed publisher
    ..The most active compounds were biochemically tested for their activity on mu, delta, and kappa opioid receptors. ..
  20. Munro T, Berry L, Van t Veer A, Beguin C, Carroll F, Zhao Z, et al. Long-acting ? opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity. BMC Pharmacol. 2012;12:5 pubmed publisher
    ..We propose that this persistence may result from entrapment in cellular compartments such as lysosomes. ..
  21. Chai X, Guan Z, Yu S, Zhao Q, Hu H, Zou Y, et al. Design, synthesis and molecular docking studies of sinomenine derivatives. Bioorg Med Chem Lett. 2012;22:5849-52 pubmed publisher
    ..Moreover, a molecular model for the binding between compound 2v and the active site of p50 was provided on the basis of the computational docking results. ..
  22. Nagase H, Watanabe A, Nemoto T, Yamaotsu N, Hayashida K, Nakajima M, et al. Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010;20:121-4 pubmed publisher
    ..2.2]octane skeleton. KNT-63 showed profound antinociceptive effects via the kappa receptor which were as potent as that of TRK-820. ..
  23. Ou Y, Li W, Li X, Lin Z, Li M. Sinomenine reduces invasion and migration ability in fibroblast-like synoviocytes cells co-cultured with activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, CD147. Rheumatol Int. 2011;31:1479-85 pubmed publisher
    ..01). Our results point to a possible mechanism of SIN on treatment of RA is the inhibitory effect of SIN on cell invasion and migration ability, which strongly correlates with repressing the expression of CD147, MMP-2, and MMP-9. ..
  24. Andreassen T, Klepstad P, Davies A, Bjordal K, Lundström S, Kaasa S, et al. Influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients. Eur J Clin Pharmacol. 2011;67:493-506 pubmed publisher
    ..CYP3A4 inducers/inhibitors should be used with caution as these are predicted to have a significant impact on oxycodone pharmacokinetics. Other characteristics explained only minor parts of the variability of the outcomes. ..
  25. Wang A, Li Z, Yuan M, Yu A, Zhu X, Tso M. Sinomenine inhibits activation of rat retinal microglia induced by advanced glycation end products. Int Immunopharmacol. 2007;7:1552-8 pubmed
    ..Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated retinal microglia in culture. ..
  26. Wang Y, Fang Y, Huang W, Zhou X, Wang M, Zhong B, et al. Effect of sinomenine on cytokine expression of macrophages and synoviocytes in adjuvant arthritis rats. J Ethnopharmacol. 2005;98:37-43 pubmed
    ..01). In conclusion, SN decreases the mRNA expression of TNF-alpha and IL-1beta by inhibiting the NF-kappaB binding activity, which is mediated through up-regulating the IkappaB-alpha expression of PMs and synoviocytes in AA rats. ..
  27. Edwards S, Smith M. Low-level quantitation of oxycodone and its oxidative metabolites, noroxycodone, and oxymorphone, in rat plasma by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;848:264-70 pubmed
    ..Lower limits of quantitation (ng/ml) and their between-day accuracy and precision were-oxycodone, 0.9 (-0.2 and 7.8%); noroxycodone, 1.0 (0.6 and 6.2%); oxymorphone 1.0 (-1.8 and 9.5%). ..
  28. Chen S, Mi X, Wang R, Wang W, Kong W, Zhang Y, et al. Behavioral effects of sinomenine in murine models of anxiety. Life Sci. 2005;78:232-8 pubmed
    ..In the open-field test, sinomenine (160 mg/kg) decreased squares entered in mice. Thus, these findings indicated that sinomenine exhibited anxiolytic-like effect. ..
  29. Feng H, Yamaki K, Takano H, Inoue K, Yanagisawa R, Yoshino S. Effect of sinomenine on collagen-induced arthritis in mice. Autoimmunity. 2007;40:532-9 pubmed
    ..These results suggest that the anti-arthritic effect of SIN may be related to the suppression of both Th1 and Th2 immune responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses. ..
  30. Jewett D, Grace M, Jones R, Billington C, Portoghese P, Levine A. The kappa-opioid antagonist GNTI reduces U50,488-, DAMGO-, and deprivation-induced feeding, but not butorphanol- and neuropeptide Y-induced feeding in rats. Brain Res. 2001;909:75-80 pubmed
  31. Manglik A, Kruse A, Kobilka T, Thian F, Mathiesen J, Sunahara R, et al. Crystal structure of the µ-opioid receptor bound to a morphinan antagonist. Nature. 2012;485:321-6 pubmed publisher
    ..These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction. ..
  32. Wang C, Mo Z, Tu H. Effect of sinomenine on morphine dependence in isolated guinea pig ileum. Di Yi Jun Yi Da Xue Xue Bao. 2003;23:329-31 pubmed
    ..To investigate the effects of sinomenine on morphine withdrawal response and acetylchline (Ach)-induced contracture in isolated guinea pig ileum...
  33. Inan S, Dun N, Cowan A. Investigation of gastrin-releasing peptide as a mediator for 5'-guanidinonaltrindole-induced compulsive scratching in mice. Peptides. 2011;32:286-92 pubmed publisher
    ..We conclude that (a) the GRP receptor system does not mediate GNTI-induced scratching and (b) the kappa opioid system is involved, at least in part, in the scratch suppressing activity of nalfurafine. ..
  34. Li X, Yue P, Ha W, Wong D, Tin M, Wang P, et al. Effect of sinomenine on gene expression of the IL-1 beta-activated human synovial sarcoma. Life Sci. 2006;79:665-73 pubmed
    ..In conclusion, our study provides supplementary information for the further studies on the pharmacological effects of sinomenine acting on synovial sarcoma. ..
  35. Zhang G, Mo Z, Wang C. [Study on the detoxification of alcohol extracts from orientvine and its effective component on withdrawal syndromes of morphine]. Zhong Yao Cai. 2009;32:1414-8 pubmed
    ..To study the detoxification of alcohol extracts from orientvine and sinomenine on morphine-dependent animal and explore the mechanism of its effect...
  36. Bileviciute Ljungar I, Spetea M, Guo Y, Schütz J, Windisch P, Schmidhammer H. Peripherally mediated antinociception of the mu-opioid receptor agonist 2-[(4,5alpha-epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino]acetic acid (HS-731) after subcutaneous and oral administration in rats with carrageenan-induced hin. J Pharmacol Exp Ther. 2006;317:220-7 pubmed
    ..These results show that systemic (s.c. and oral) treatment with the mu-opioid agonist HS-731 produces potent and long-lasting antinociception through peripheral mechanisms in rats with carrageenan-induced hindpaw inflammation. ..
  37. Wang Q, Li X. Immunosuppressive and anti-inflammatory activities of sinomenine. Int Immunopharmacol. 2011;11:373-6 pubmed publisher
    ..This review will summarize its potential effects, mechanisms and applications...
  38. Liu Z, Chan K, Zhou H, Jiang Z, Wong Y, Xu H, et al. The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro. Life Sci. 2005;77:3197-209 pubmed
    ..This result suggests that sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property. ..
  39. Zhang A, Xiong W, Hilbert J, DeVita E, Bidlack J, Neumeyer J. 2-aminothiazole-derived opioids. Bioisosteric replacement of phenols. J Med Chem. 2004;47:1886-8 pubmed
    A series of aminothiazole-derived morphinans, benzomorphans, and morphine were synthesized...
  40. Ju X, Deng M, Ao Y, Yu C, Wang J, Yu J, et al. Protective effect of sinomenine on cartilage degradation and chondrocytes apoptosis. Yakugaku Zasshi. 2010;130:1053-60 pubmed
    ..Thus, SIN has the protective capacity to antagonize cartilage degradation and chondrocyte apoptosis, which suggest that SIN may act as an agent for pharmacological intervention in the progress of OA. ..
  41. Xu M, Liu L, Qi C, Deng B, Cai X. Sinomenine versus NSAIDs for the treatment of rheumatoid arthritis: a systematic review and meta-analysis. Planta Med. 2008;74:1423-9 pubmed publisher
    ..31). In conclusion, SIN may be a valuable remedy to treat RA clinically, although current evidence needs to be further verified by more high-quality trials. ..
  42. Inan S, Dun N, Cowan A. Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5'-guanidinonaltrindole-induced scratching models in mice: behavioral and neuroanatomical evidence. Eur J Pharmacol. 2009;616:141-6 pubmed publisher
    ..Our results highlight the antipruritic properties of lidocaine and argue for its comprehensive clinical testing against pruritic states. ..
  43. Chen W, Zhou Y, Kang J, Li Q, Feng X. [Study on pharmacokinetics and absolute bioavailability of sinomenine in beagle dogs]. Zhongguo Zhong Yao Za Zhi. 2009;34:468-71 pubmed
    ..7 +/- 120.2) min and (93.32 +/- 82.08) mg x min x L(-1). The absolute bioavailability for oral use was (30.46 +/- 4.24)%. The absolute bioavailability of sinomenine is low, and the elimination of sinomenine tablet is fast. ..
  44. Cheng H, Xia B, Guo Q, Zhang L, Wang F, Jiang L, et al. Sinomenine attenuates 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice. Int Immunopharmacol. 2007;7:604-11 pubmed
    ..Our findings suggest that sinomenine attenuates TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha and IFN-gamma production caused by TNBS. ..
  45. Yao Y, Tan Z, Hu Z, Guo X, Cheng Z, Wang L, et al. Determination of sinomenine in human plasma by HPLC/ESI/ion trap mass spectrum. Clin Chim Acta. 2005;356:212-7 pubmed
    ..The method is simple, rapid, sensitive, specific, and accurate enough for determination of sinomenine in human plasma and may be used to investigate the metabolism and pharmacokinetics of sinomenine. ..
  46. Zhao Y, Li J, Yu K, Liu Y, Chen X. Sinomenine inhibits maturation of monocyte-derived dendritic cells through blocking activation of NF-kappa B. Int Immunopharmacol. 2007;7:637-45 pubmed
    ..The findings indicate the potency for sinomenine to be generally used in DCs-mediated autoimmune diseases. ..
  47. Chen D, Wong C, Leung P, Fung K, Lau C, Lau C, et al. Anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on tumor necrosis factor-?-activated human fibroblast-like synoviocytes in rheumatoid arthritis. J Ethnopharmacol. 2011;137:457-68 pubmed publisher
    ..Our results therefore provide a new insight into the differential anti-inflammatory activities of sinomenine and LMS through the suppression of TNF-?-activated FLS by modulating distinct intracellular signaling pathways in RA. ..
  48. Liu Z, Zheng J, Yang L, Yi L, Hu B. [Effects of sinomenine on NO/nNOS system in cerebellum and spinal cord of morphine-dependent and withdrawal mice]. Sheng Li Xue Bao. 2007;59:285-92 pubmed
  49. Wang Y, Zhou L, Li R. [Study progress in Sinomenium acutum (Thunb.) Rehd. et Wils]. Zhong Yao Cai. 2002;25:209-11 pubmed
    ..Rehd. et Wils. An expectation for the further development and utilization of this plant was put forward...
  50. Negus S, Mello N, Linsenmayer D, Jones R, Portoghese P. Kappa opioid antagonist effects of the novel kappa antagonist 5'-guanidinonaltrindole (GNTI) in an assay of schedule-controlled behavior in rhesus monkeys. Psychopharmacology (Berl). 2002;163:412-9 pubmed
    ..Relative to the prototype kappa antagonist nor-binaltorphimine, GNTI may have some advantages as a tool for the study of kappa receptor-mediated processes. ..
  51. Neumeyer J, Gu X, van Vliet L, DeNunzio N, Rusovici D, Cohen D, et al. Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan. Bioorg Med Chem Lett. 2001;11:2735-40 pubmed
    ..All of these novel derivatives showed a preference for the mu and kappa versus delta binding. ..
  52. He X, Wang J, Guo Z, Liu Q, Chen T, Wang X, et al. Requirement for ERK activation in sinomenine-induced apoptosis of macrophages. Immunol Lett. 2005;98:91-6 pubmed
    ..Therefore, induction of macrophage apoptosis through ERK activation may be one of mechanisms by which SN exhibits its immunosuppressive function. ..
  53. Mo Z, Leung W, Yung K. [Changes in cAMP and cGMP levels in neonatal rat histaminergic neurons of tuberomammillary nucleus following 48-hour morphine exposure and effects of sinomenine intervention]. Di Yi Jun Yi Da Xue Xue Bao. 2005;25:1105-8 pubmed
    ..Sinomenine can significantly reduce the cAMP level and enhance cGMP level of morphine-dependent TM neurons precipitated by naloxone, which results in a near-normal ratio of cAMP and cGMP. ..