Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction
AbstractDamage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM) and gadolinium (300 μM). The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.
Altamura, M., Meini, S., Quartara, L., & Maggi, C. (1999). Nonpeptide antagonists for kinin receptors. Regulatory Peptides, 80, 13–26. >> doi.org/10.1016/S0167-0115(99)00003-8
Alves, F., Oliva, M., & Miranda, A. (2015). Conformational and biological properties of Bauhinia bauhinioides kallikrein inhibitor fragments with bradykinin-like activities. Journals of Peptide Science, 21, 495–500. >> doi.org/10.1002/psc.2766
Andronati, S., Kabanova, T., Pavlovskij, V., Andronati, K., & Bachins’kij, S. (2009). Ligandy bradikininovyh receptorov kak potencial’nie anal’geti¬cheskie i protivovospalitel’nie sredstva. Zhurnal Organichnoji ta Farma¬cevtichnoji Khimiji, 28(4), 70–76 (in Russian).
Baron, R., Binder, A., & Wasner, G. (2010). Neuropathic pain: Diagnosis, pathophysiological mechanisms, and treatment. The Lancet Neurology, 9(8), 807–819. >> doi.org/10.1016/S1474-4422(10)70143-5
Bartusch, S., Sanders, B., D’Alessio, J., & Jernigan, J. (1996). Clonazepam for the treatment of lancinating phantom limb pain. The Clinical Journal of Pain, 12, 59–62. >> doi.org/10.1097/00002508-199603000-00011
Becker, D., & Reed, K. (2006). Essentials of local anesthetic pharmacology. Anesthesia Progress, 93(3), 98–109. >> doi.org/10.2344/0003-3006(2006)53%5b98:EOLAP%5d2.0.CO;2
Bergson, P., Lipkind, G., Lee, S., Duban, M., & Hanck, D. (2011). Verapamil block of T-type calcium channels. Molecular Pharmacology, 79(3), 411–419. >> doi.org/10.1124/mol.110.069492
Burdyga, T., & Kosterin, S. (1991). Kinetic analysis of smooth muscle relaxation. General Physiology and Biophysics, 10, 589–598.
Chou, R., & Huffman, L. (2007). Medications for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Annals of Internal Medicine, 147, 505–514. >> doi.org/10.7326/0003-4819-147-7-200710020-00008
Dziadulewicz, E., Brown, M., Dunstan, A., Lee, W., Said, N., & Garratt, P. (1999). The design of non-peptide human bradykinin B2 receptor antagonists employing the benzodiazepine peptidomimetic scaffold. Bioorganic and Medicinal Chemistry Letters, 9(3), 463–468. >> doi.org/10.1016/S0960-894X(99)00015-3
Garcia, P., Kolesky, S., & Jenkins, A. (2010). General anesthetic actions on GABAA receptors. Current Neuropharmacology, 8, 2–9. >> doi.org/10.2174/157015910790909502
Gierthmuhlen, J., Binder, A., & Baron, R. (2014). Mechanism-based treatment in complex regional pain syndromes. Nature Reviews. Neurology, 10(9), 518–528. >> doi.org/10.1038/nrneurol.2014.140
Higashida, H., Streaty, R., Klee, W., & Nirenberg, M. (1986). Bradykinin-activated transmembrane signals are coupled via No or Ni to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells. Proceedings of the National Academy of Sciences of the United States of America, 83, 942–946. >> doi.org/10.1073/pnas.83.4.942
Howard, P., Twycross, R., Shuster, J., & Mihalyo, M. (2014). Benzodiaze¬pines. Journal of Pain and Symptom Management, 47(5), 955–964. >> doi.org/10.1016/j.jpainsymman.2014.03.001
Hugel, H., Ellershaw, J., & Dickman, A. (2003). Clonazepam as an adjuvant analgesic in patients with cancer-related neuropathic pain. Journal of Pain and Symptom Management, 26, 1073–1074. >> doi.org/10.1016/j.jpainsymman.2003.09.005
Kam, Y., Ro, J., Kim, H., & Choo, H. (2005). Antagonistic effects of novel non-peptide chlorobenzhydryl piperazine compounds on contractile response to bradykinin in the guinea-pig ileum. European Journal of Pharmacology, 523, 143–150. >> doi.org/10.1016/j.ejphar.2005.09.010
Kerstman, E., Ahn, S., Battu, S., Tariq, S., & Grabois, M. (2013). Neuropathic pain. In: M. Barnes, D. Good, Handbook of clinical neurology. Neurological Rehabilitation. Elsevier B.V., 110, pp. 175–187. >> doi.org/10.1016/c2009-0-39170-9
Ludwig, J., & Baron, R. (2004). Complex regional pain syndrome: An inﬂam¬matory pain condition? Drug Discovery Today: Disease Mechanisms, 4(1), 449–455. >> doi.org/10.1016/j.ddmec.2004.11.013
Malasics, А., Boda, D., Valisko, M., Henderson, D., & Gillespie, D. (2010). Simulations of calcium channel block by trivalent cations: Gd3+ competes with permeant ions for the selectivity filter. Biochimica et Biophysica Acta, 1798(11), 2013–2021. >> doi.org/10.1016/j.bbamem.2010.08.001
Marcon, R., Claudino, R., Dutra, R., Bento, A., Schmidt, E., Bouzon, Z., Sordi, R., Morais, R., Pesquero, J., & Calixto, J. (2013). Exacerbation of DSS-induced colitis in mice lacking kinin B1 receptors through compensatory up-regulation of kinin B2 receptors: The role of tight junctions and intestinal homeostasis. British Journal of Pharmacology, 168(2), 389–402. >> doi.org/10.1111/j.1476-5381.2012.02136.x
Pesquero, J., & Bader, M. (1998). Molecular biology of the kallikrein-kinin system: from structure to function. Brazilian Journal of Medical and Biological Research, 31, 1197–1203. >> doi.org/10.1590/S0100-879X1998000900013
Pleuvry, B. (2008). Mechanism of action of general anaesthetic drugs. Anaesthesia and Intensive Care Medicine, 9(4), 152–153. >> doi.org/10.1016/j.mpaic.2007.08.004
Scholz, A. (2002). Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels. British Journal of Anaesthesia, 89(1), 52–61. >> doi.org/10.1093/bja/aef163
Stadnicki, A. (2011). Intestinal tissue kallikrein-kinin system in Inﬂammatory bowel disease. Inflammatory Bowel Diseases, 17(2), 645–654. >> doi.org/10.1002/ibd.21337
Watkins, L., & Maier, S. (2002). Beyond neurons: Evidence that immune and glial cells contribute to pathological pain states. Physiological Reviews, 82(4), 981–1011. >> doi.org/10.1152/physrev.00011.2002
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