Histamine plays its function through binding with four already known histamine receptors, designed as H1-H4. It is assumed, that the youngest member of the family – histamine H4 receptor (H4R), which was discovered and cloned in 2000/2001 by several independent research groups [1], is involved in inflammatory processes and immune responses, because of its mainly expression in various cells of the immune system (monocytes, mast cells, dendritic cells, eosinophils and basophils) [2]. Potential therapeutic effects of H4R antagonists/inverse agonists in animal models of acute inflammations, allergic rhinitis, asthma or pruritus were confirmed [3]. As physiological role of H4R is not clear - new, potent and selective ligands are required to investigate its action. Among H4R ligands already described in the literature and patent data there can be found a large group of triazine derivatives [4,5]. The aim of this study was to evaluate in vivo activity of five 4-(4- methylpiperazin-1-yl)-1,3,5-triazine derivatives (KB-4, KB-30, JN-38, TR-11 and TR-40), Compounds were tested in croton oil-induced ear edema model and ear pruritus model in vivo in mice. Compounds examined in the presented studies were selected from the library of compounds synthesized in our Department. The obtained results showed that pre-treatment with KB-4, KB-30 or TR-11 has strong to moderate influence on ear edema and pruritus. Among the tested compounds, KB-4 and TR-11 seem to have the most favourable profile, combining a good affinity at the human histamine H4 receptor with a high efficacy in the intact animal. The results in detail will be presented and discussed. Acknowledgments: This work was kindly supported by National Science Center DEC-2011/02/A/NZ4/00031 and GLISTEN: COST Action CM1207. References: 1. Nguyen, T. et al.: Mol. Pharmacol. 2001, 59(3): 427-433. 2. Walter, M. et al.: Eur. J. Pharmacol. 2011, 668(1-2): 1-5. 3. Tiligada, E. et al.: Expert Opin. Investig. Drugs. 2009, 18(10): 1519-1531. 4. Kiss, R.; Reserű, G.M.: Expert Opin. Ther. Pat. 2012, 22(3): 205-221.

Histamine H4 receptor affinity of 1,3,5-triazine derivatives / Kamińska, K.; Więcek, M.; Adami, Maristella; Stark, H.; Kieć Kononowicz, K.. - (2015), pp. 148-148.

Histamine H4 receptor affinity of 1,3,5-triazine derivatives.

ADAMI, Maristella;
2015-01-01

Abstract

Histamine plays its function through binding with four already known histamine receptors, designed as H1-H4. It is assumed, that the youngest member of the family – histamine H4 receptor (H4R), which was discovered and cloned in 2000/2001 by several independent research groups [1], is involved in inflammatory processes and immune responses, because of its mainly expression in various cells of the immune system (monocytes, mast cells, dendritic cells, eosinophils and basophils) [2]. Potential therapeutic effects of H4R antagonists/inverse agonists in animal models of acute inflammations, allergic rhinitis, asthma or pruritus were confirmed [3]. As physiological role of H4R is not clear - new, potent and selective ligands are required to investigate its action. Among H4R ligands already described in the literature and patent data there can be found a large group of triazine derivatives [4,5]. The aim of this study was to evaluate in vivo activity of five 4-(4- methylpiperazin-1-yl)-1,3,5-triazine derivatives (KB-4, KB-30, JN-38, TR-11 and TR-40), Compounds were tested in croton oil-induced ear edema model and ear pruritus model in vivo in mice. Compounds examined in the presented studies were selected from the library of compounds synthesized in our Department. The obtained results showed that pre-treatment with KB-4, KB-30 or TR-11 has strong to moderate influence on ear edema and pruritus. Among the tested compounds, KB-4 and TR-11 seem to have the most favourable profile, combining a good affinity at the human histamine H4 receptor with a high efficacy in the intact animal. The results in detail will be presented and discussed. Acknowledgments: This work was kindly supported by National Science Center DEC-2011/02/A/NZ4/00031 and GLISTEN: COST Action CM1207. References: 1. Nguyen, T. et al.: Mol. Pharmacol. 2001, 59(3): 427-433. 2. Walter, M. et al.: Eur. J. Pharmacol. 2011, 668(1-2): 1-5. 3. Tiligada, E. et al.: Expert Opin. Investig. Drugs. 2009, 18(10): 1519-1531. 4. Kiss, R.; Reserű, G.M.: Expert Opin. Ther. Pat. 2012, 22(3): 205-221.
Histamine H4 receptor affinity of 1,3,5-triazine derivatives / Kamińska, K.; Więcek, M.; Adami, Maristella; Stark, H.; Kieć Kononowicz, K.. - (2015), pp. 148-148.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2815588
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact