Poly(ethylene terephthalate) was depolymerised under supercritical ethanol, 98 wt% of diethylterephthalate was obtained after 45 min, by adding [Bmim][BF4] as catalyst.

The marine snail peptide ziconotide (x-conotoxin MVIIA) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side-effects of spider peptide Pha1b in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B16-F10 cells into the hind paw of C57BL ⁄ 6 mice. After 14 days, painful hypersensitivity was detected and Pha1b or x-conotoxin MVIIA (10-100 pmol ⁄ site) was intrathecally injected to evaluate the development of antinociception and side-effects in control and morphine-tolerant mice. The treatment with Pha1b or x-conotoxin MVIIA fully reversed cancer-related painful hypersensitivity, with long-lasting results, at effective doses 50% of 48 (32-72) or 33 (21-53) pmol ⁄ site, respectively. Pha1b produced only mild adverse effects, whereas x-conotoxin MVIIA induced dose-related side-effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol ⁄ site). In addition, we observed that Pha1b was capable of controlling cancer-related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 AE 5% of inhibition). In this study, Pha1b was as efficacious as x-conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid-tolerant mice, indicating that Pha1b has a good profile for the treatment of cancer pain in patients. (Cancer Sci 2013; 104: 1226-1230

The transient receptor potential vanilloid 1 (TRPV1) receptor is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction also had antioedematogenic effect. Among the compounds isolated from the dichloromethane fraction, only ␣-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, ␣-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. ␣-Spinasterol was able to displace [ 3 H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and ␣-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with ␣-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, ␣-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and ␣-spinasterol did not affect body temperature or locomotor activity. In conclusion, ␣-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.

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