Chronic pain is a widely recognized unmet medical target and the research for new analgesic agents is being intensively investigated by the pharmaceutical industry. Among the Transient Receptor Potential (TRP) channels, the TRPV1 (subfamily Vanilloid, Type-1) is considered as a highly validated pain target being abundantly expressed in sensory neurons and also in higher brain structures involved during pain processing and neurogenic inflammatory response.[1,2] Responsible for binding the natural pungent principle of capsicum, the capsaicin, and activated by endogenous arachidonic acid-derived lipids called “Endovanilloids”, this receptor plays an important role in several human pathological conditions, such as inflammatory, visceral, cancer and neuropathic pain. Considering some common structural features inside the very extensive chemical diversity of known agonists and antagonists, we have identified a new class of TRPV1 effective ligands, derived from a 4-(thiophen-2-yl)butanoic acid amide moiety, endowed with a significant agonist activity. [1] J.F. Sanchez, J.E. Krause, D.N. Cortright Neuroscience, 2001, 107, 373-381. [2] A. Szallasi, V. Di Marzo Trends Neurosci., 2000, 23, 491-497.
Identification of new potent TRPV1 ligands showing analgesic properties
AIELLO, Francesca;GRANDE, Fedora;GAROFALO A;
2014-01-01
Abstract
Chronic pain is a widely recognized unmet medical target and the research for new analgesic agents is being intensively investigated by the pharmaceutical industry. Among the Transient Receptor Potential (TRP) channels, the TRPV1 (subfamily Vanilloid, Type-1) is considered as a highly validated pain target being abundantly expressed in sensory neurons and also in higher brain structures involved during pain processing and neurogenic inflammatory response.[1,2] Responsible for binding the natural pungent principle of capsicum, the capsaicin, and activated by endogenous arachidonic acid-derived lipids called “Endovanilloids”, this receptor plays an important role in several human pathological conditions, such as inflammatory, visceral, cancer and neuropathic pain. Considering some common structural features inside the very extensive chemical diversity of known agonists and antagonists, we have identified a new class of TRPV1 effective ligands, derived from a 4-(thiophen-2-yl)butanoic acid amide moiety, endowed with a significant agonist activity. [1] J.F. Sanchez, J.E. Krause, D.N. Cortright Neuroscience, 2001, 107, 373-381. [2] A. Szallasi, V. Di Marzo Trends Neurosci., 2000, 23, 491-497.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
