α-Truxillic acid can be formed by the dimerization of two molecules of α-trans-cinnamic acid. [1] It is related to incarvillateine, a natural antinociceptive compound derived from the Asian herb I. sinensis. [2] α-Truxillic acid and some of its derivatives significantly block inflammatory pain while having little effect on neurogenic pain, as indicated by the formalin test in mice. [2] [3] Related compounds, like SB-FI-26 , bind fatty acid binding protein 5 (FABP5). [4] This may be related to pain suppression, since FABP5 acts as a transporter of the endocannabinoid anandamide. [5] While certain derivatives of α-truxillic acid can directly activate peroxisome proliferator-activated receptor γ, α-truxillic acid has no such activity. [6]
Reference:
[1]. Benedict, J.B., and Coppens, P. Kinetics of the single-crystal to single-crystal two-photon photodimerization of α-trans-cinnamic acid to α-truxillic acid. J.Phys.Chem.A. 113(13), 3116-3120 (2009).
[2]. Chi, Y.M., Nakamura, M., Yoshizawa, T., et al. Anti-inflammatory activities of α-truxillic acid derivatives and their monomer components. Biological and Pharmaceutical Bullentin 28(9), 1776-1778 (2005).
[3]. Chi, Y.M., Nakamura, M., Zhao, X.Y., et al. Antinociceptive activities of α-truxillic acid and β-truxillic acid derivatives. Biological and Pharmaceutical Bullentin 29(3), 580-584 (2006).
[4]. Berger, W.T., Ralph, B.P., Kaczocha, M., et al. Targeting fatty acid binding protein (FABP) anandamide transporters - a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS One 7(12), (2012).
[5]. Kaczocha, M., Glaser, S.T., and Deutsch, D.G. Identification of intracellular carriers for the endocannabinoid anandamide. Proceedings of the National Academy of Sciences of the United States of America 106(15), 6375-6380 (2009).
[6]. Steri, R., Rupp, M., Proschak, E., et al. Truxillic acid derivatives act as peroxisome proliferator-activated receptor γ activators. Bioorganic & Medicinal Chemistry Letters 20(9), 2920-2923 (2010).