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SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) inhibits TNF-alpha production through the activation of capsaicin-sensitive afferent neurons mediated via transient receptor potential vanilloid 1 in vivo.
Eur J Pharmacol. 2008 Jul 07; 588(2-3):309-15.EJ

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is known to play a crucial role in the pathogenesis of rheumatoid arthritis. In the present study, we demonstrate the effects of SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea), a novel orally active inhibitor of TNF-alpha production, in animal models, and its mechanism of action on TNF-alpha production. SA13353 significantly inhibited lipopolysaccharide (LPS)-induced TNF-alpha production in a dose-dependent manner in rats. Moreover, SA13353 exhibited a binding affinity for the rat vanilloid receptor and increased neuropeptide release from the rat dorsal root ganglion neurons. However, its effects were blocked by pretreatment with the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. The ability of SA13353 and capsaicin to inhibit LPS-induced TNF-alpha production was eliminated by sensory denervation or capsazepine pretreatment in vivo. Although they inhibited LPS-induced TNF-alpha production in mice, these effects were not observed in TRPV1 knockout mice. SA13353 provoked the release of neuropeptides without nerve inactivation, even when chronically administered to rats. These results suggest that SA13353 inhibits TNF-alpha production through activation of capsaicin-sensitive afferent neurons mediated via TRPV1 in vivo. Post-onset treatment of SA13353 strongly reduced the hindpaw swelling and joint destruction associated with collagen-induced arthritis in rats. Thus, SA13353 is expected to be a novel anti-arthritic agent with a unique mechanism of action.

Authors+Show Affiliations

Research and Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma-shi, Nara 630-0101, Japan. masaaki.murai@santen.co.jp <masaaki.murai@santen.co.jp>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18508045

Citation

Murai, Masaaki, et al. "SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) Inhibits TNF-alpha Production Through the Activation of Capsaicin-sensitive Afferent Neurons Mediated Via Transient Receptor Potential Vanilloid 1 in Vivo." European Journal of Pharmacology, vol. 588, no. 2-3, 2008, pp. 309-15.
Murai M, Tsuji F, Nose M, et al. SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) inhibits TNF-alpha production through the activation of capsaicin-sensitive afferent neurons mediated via transient receptor potential vanilloid 1 in vivo. Eur J Pharmacol. 2008;588(2-3):309-15.
Murai, M., Tsuji, F., Nose, M., Seki, I., Oki, K., Setoguchi, C., Suhara, H., Sasano, M., & Aono, H. (2008). SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) inhibits TNF-alpha production through the activation of capsaicin-sensitive afferent neurons mediated via transient receptor potential vanilloid 1 in vivo. European Journal of Pharmacology, 588(2-3), 309-15. https://doi.org/10.1016/j.ejphar.2008.04.037
Murai M, et al. SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) Inhibits TNF-alpha Production Through the Activation of Capsaicin-sensitive Afferent Neurons Mediated Via Transient Receptor Potential Vanilloid 1 in Vivo. Eur J Pharmacol. 2008 Jul 7;588(2-3):309-15. PubMed PMID: 18508045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea) inhibits TNF-alpha production through the activation of capsaicin-sensitive afferent neurons mediated via transient receptor potential vanilloid 1 in vivo. AU - Murai,Masaaki, AU - Tsuji,Fumio, AU - Nose,Masafumi, AU - Seki,Iwao, AU - Oki,Kenji, AU - Setoguchi,Chikako, AU - Suhara,Hiroshi, AU - Sasano,Minoru, AU - Aono,Hiroyuki, Y1 - 2008/04/20/ PY - 2007/12/10/received PY - 2008/03/31/revised PY - 2008/04/09/accepted PY - 2008/5/30/pubmed PY - 2008/9/3/medline PY - 2008/5/30/entrez SP - 309 EP - 15 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 588 IS - 2-3 N2 - Tumor necrosis factor-alpha (TNF-alpha) is known to play a crucial role in the pathogenesis of rheumatoid arthritis. In the present study, we demonstrate the effects of SA13353 (1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea), a novel orally active inhibitor of TNF-alpha production, in animal models, and its mechanism of action on TNF-alpha production. SA13353 significantly inhibited lipopolysaccharide (LPS)-induced TNF-alpha production in a dose-dependent manner in rats. Moreover, SA13353 exhibited a binding affinity for the rat vanilloid receptor and increased neuropeptide release from the rat dorsal root ganglion neurons. However, its effects were blocked by pretreatment with the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. The ability of SA13353 and capsaicin to inhibit LPS-induced TNF-alpha production was eliminated by sensory denervation or capsazepine pretreatment in vivo. Although they inhibited LPS-induced TNF-alpha production in mice, these effects were not observed in TRPV1 knockout mice. SA13353 provoked the release of neuropeptides without nerve inactivation, even when chronically administered to rats. These results suggest that SA13353 inhibits TNF-alpha production through activation of capsaicin-sensitive afferent neurons mediated via TRPV1 in vivo. Post-onset treatment of SA13353 strongly reduced the hindpaw swelling and joint destruction associated with collagen-induced arthritis in rats. Thus, SA13353 is expected to be a novel anti-arthritic agent with a unique mechanism of action. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18508045/SA13353__1_[2__1_Adamantyl_ethyl]_1_pentyl_3_[3__4_pyridyl_propyl]urea__inhibits_TNF_alpha_production_through_the_activation_of_capsaicin_sensitive_afferent_neurons_mediated_via_transient_receptor_potential_vanilloid_1_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00466-4 DB - PRIME DP - Unbound Medicine ER -