Disease relevance of Lopac-C-191

• Further examinations revealed that TRPV1-induced toxicity was accompanied by increases in intracellular Ca(2+), and mitochondrial damage; these effects were inhibited by capsazepine, I-RTX, and the intracellular Ca(2+) chelator BAPTA-AM [1].
• Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is inhibited by the BK(Ca) channel inhibitor charybdotoxin, but not by the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester or by the vanilloid VR1 receptor antagonist capsazepine [2].
• Intraperitoneal administration of the competitive TRPV1 antagonist capsazepine inhibited hyperalgesia induced by tumor cell-inoculation in either plantar- or thigh-inoculated animals [3].
• AT-induced effects including reduction of hypotension (n = 5) and inhibition of induction of iNOS (n = 4 or 5) and TNF- alpha (n = 5) in the lungs of endotoxin-treated animals were completely reversed by pretreatment with capsazepine (CPZ) (n = 4 or 5), a vanilloid receptor antagonist, or CGRP(8-37), a CGRP receptor antagonist (n = 4 or 5) [4].
• CONCLUSIONS: In the isolated guinea pig heart, moderate acidosis is associated with CGRP release dependent on influx of extracellular Ca2+ and formation of PGI2, with subsequent stimulation of capsazepine sensitive receptors [5].

Psychiatry related information on Lopac-C-191

• First, we explored whether the inhibitory effects of anandamide on motor activity and dopaminergic transmission were reversed by capsazepine, an antagonist for vanilloid-like receptors [6].

High impact information on Lopac-C-191

• In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1), anandamide induced a capsazepine-sensitive current in whole cells and isolated membrane patches [7].
• Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion [8].
• In VR1+/+ mice, this effect is inhibited by the VR1 antagonist capsazepine [9].
• 0. These similarities include kinetics, reversal potentials, responses to Ca2+, and inhibition by ruthenium red and capsazepine [10].
• The results of experiments using LNCaP cells, the TRPM8 antagonist capsazepine, and small interference RNA targeted to TRPM8 indicate that TRPM8 is required for cell survival [11].

Chemical compound and disease context of Lopac-C-191

• Capsaicin (10 nmol)-induced hyperalgesia was blocked by capsazepine (0.5-5 nmol) [12].
• This bradycardia was dose-dependently diminished by the selective vanilloid receptor antagonist capsazepine (0.3-3 micromol/kg) and the nonselective inhibitor of these receptors, ruthenium red (1-10 micromol/kg) [13].
• In separate experiments, the hypothermia caused by WIN 55212-2 (5 mg/kg, i.m.), a cannabinoid agonist, was not significantly altered by capsazepine (10 and 30 mg/kg, i.p.) or SB 366791 (2 mg/kg, i.p.), a novel TRPV1 antagonist [14].
• Nw-nitro-L-arginine methyl ester (L-NAME), glibenclamide, and capsazepine inhibited VOA-induced hypotension [15].

Biological context of Lopac-C-191

• In this system, capsaicin and PPAHV induced cell death by an apparent necrotic mechanism, which was selectively inhibited by the competitive vanilloid receptor antagonist capsazepine [16].
• The effects of capsazepine are consistent with reversible blockade of the VR1 receptor to abolish C fibre-mediated reflex bronchoconstriction [17].
• The RAR-like fibres response to the approximately 3 s acid treatment was not affected by a vanilloid receptor 1 (VR1) antagonist, capsazepine (10 microM), and was rapidly inactivating (action potential discharge terminated before the acid administration was completed) [18].
• Apoptosis was completely prevented by inhibiting TRPV1 receptors with capsazepine or by removing extracellular calcium or in sensory neurons from TRPV1(-/-) mice [19].
• Conceivably, capsazepine interacts with binding sites for capsaicin, acting as a partial agonist/antagonist, while ruthenium red interacts with capsaicin-operated cation channels [20].

Anatomical context of Lopac-C-191

• In sensory neurons, OEA-induced Ca2+ rises that were selective for capsaicin-sensitive cells, inhibited by the TRPV1 blocker, capsazepine, and occurred in a PKC-dependent manner [21].
• The inward currents at a holding potential of -60 mV in hENaCdeltabetagamma-expressing oocytes were markedly enhanced by the application of capsazepine (> or =1 microM), and the capsazepine-induced current was mostly abolished by the addition of 100 microM amiloride [22].
• Furthermore, activation of TRPV1 receptors seems to play a role of stabilization of the plasma membranes in capacitated sperm, as demonstrated by the high incidence of spontaneous AR occurring during the cultural period when TRPV1 activity was antagonized by capsazepine [23].
• The competitive vanilloid receptor antagonist capsazepine inhibited [(3)H]RTX binding to HEK293/VR1 cells with a K(i) value of 6.2 microM and binding to DRG membranes with a K(i) value of 8.6 microM [24].
• Finally, JYL1421 and KJM429 had little or no effect on ATP-induced calcium uptake in CHO cells lacking rVR1, unlike capsazepine [25].

Associations of Lopac-C-191 with other chemical compounds

• A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery [26].
• CT responses were recorded in the presence of Bz (a specific blocker of the epithelial Na(+) channel [ENaC]) or the vanilloid receptor-1 (VR-1) antagonists capsazepine or SB-366791, which also block the Bz-insensitive salt taste receptor, a VR-1 variant [27].
• First, we tried to block the effects of AM404 with selective antagonists for the CB1 or VR1 receptors, i.e. SR141716A and capsazepine, respectively [28].
• 4. Lactic acid-evoked increases in RL were unaffected by VR1 blockade with capsazepine, consistent with a separate lactic acid-induced reflex mechanism [17].
• METHODS: A metabolically stable analog of AEA, methanandamide (MethA, 300 nmol/kg per min), was infused into the left renal medulla of anesthetized Wistar rats with or without a selective TRPV1 antagonist, capsazepine (Capz, 150 nmol/kg per min) or a selective cannabinoid receptor 1 (CB1) antagonist, AM251 (Am, 150 nmol/kg per min) [29].

Gene context of Lopac-C-191

• In our psychophysical experiments, direct infusion of acidic solutions (pH > or = 6.0) into human skin caused localized pain, which was blocked by amiloride, an inhibitor of ASICs, but not by capsazepine, an inhibitor of VR1 [30].
• VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ) [31].
• In conclusion, capsazepine acts on ENaCdelta and acts together with protons [22].
• Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis [32].
• In these cells, PCs induced an increase in [Ca2+]i that was inhibited by capsazepine, a TRPV1 antagonist, and/or by amiloride, an ASIC antagonist [33].

Analytical, diagnostic and therapeutic context of Lopac-C-191

• Similarly, in the partial sciatic nerve ligation model of neuropathic pain, capsazepine was surprisingly effective in the guinea pig, producing up to 80% reversal of mechanical hyperalgesia (1-30 mg/kg s.c.) but had no effect in the rat or mouse [34].
• 2. The anandamide-induced pressor effect was not modified by the antagonists of cannabinoid CB(1) and vanilloid TRPV(1) receptors, SR 141716A (3 micromol kg(-1)) and capsazepine (1 micromol kg(-1)), respectively, by bilateral vagotomy and by pithing [35].
• These increases were significantly inhibited by subcutaneous injection of capsazepine (CPZ), a vanilloid receptor antagonist, and by functional denervation of capsaicin-sensitive sensory neurons induced by the administration of high-dose capsaicin [36].
• Intradermal injection of capsazepine, a capsaicin-receptor antagonist, significantly reduced the number of cells exhibiting Fos-like immunoreactivity, significantly increased the paw-withdrawal latency, but did not decrease inflammation induced by carrageenan injection [37].
• Arvanil (i.t. administration) induced analgesia in the tail-flick test that was not blocked by either SR141716A or the vanilloid VR(1) antagonist capsazepine [38].

References