morphinans and tetramethylpyrazine

Topics: Administration, Cutaneous; Animals; Drugs, Chinese Herbal; Lactates; Morphinans; Plants, Medicinal; Pyrazines; Skin Absorption

Management of chronic pain is restricted by the lack of effective tools. This study evaluated the efficacies of sinomenine combined gabapentin or ligustrazine hydrochloride in treating peripheral and central chronic neuropathic pain. The study was conducted in mice with photochemically induced sciatic nerve injury, and in rats with photochemically induced spinal cord injury. For assessing the effectiveness of combined therapy, sinomenine, gabapentin or ligustrazine hydrochloride was injected intraperitoneally (i.p.), and pain behavioral tests were performed. At sub-effective dosages, pre-administration of sinomenine (for 60 min) plus gabapentin or ligustrazine hydrochloride, generated significant anti-allodynic effects in mice or rats with peripheral or central neuropathic pain. However, these effects were abolished when gabapentin or ligustrazine hydrochloride was pre-administered, and then sinomenine was given 60 min later. The combined efficacies of sinomenine and gabapentin or ligustrazine hydrochloride, cannot be blocked or reversed by the naloxone, suggesting the underlying mechanism is not mediated by opioid receptors. Moreover, following repeated treatments, sinomenine and gabapentin combination increased the baseline mechanical threshold, while generating prolonged analgesia, without introducing notable side effects. Sinomenine can enhance the efficacy of gabapentin or ligustrazine hydrochloride in rodent models of peripheral or central neuropathic pain, without introducing tolerance or other notable side effects. Findings of current study suggest that combing sinomenine and gabapentin or ligustrazine hydrochloride could be highly beneficial in neuropathic pain therapies.

Topics: Analgesics; Animals; Disease Models, Animal; Drug Synergism; Gabapentin; Male; Mice; Mice, Inbred C57BL; Morphinans; Neuralgia; Peripheral Nerve Injuries; Pyrazines; Spinal Cord Injuries

The aim of the research was to investigate the antiendotoxin effects of Sinomenine, Fangchinoline, Stachydrine, Chuanxionggzine, Oxymartrine and Evodiamine. Endothelial cells were challenged with 1 μg/mL LPS for 3 h then treated respectively with six alkaloids at three concentrations (1, 5 and 10 μg/mL). The cells were incubated at 37°C in a cell incubator for 21 h. The supernatants were collected and analyzed the levels of interleukin-1α (IL-1α), thromboxane B(2) (TXB(2)), endothelin-1 (ET-1) and E-selectin by ELISA kits. The results revealed that Sinomenine, Oxymartrine and Evodiamine inhibited the production of IL-1α; Stachydrine, Chuanxionggzine and Evodiamine inhibited the secretion of TXB(2); Sinomenine and Oxymartrine down-regulated ET-1 expression; Fangchinoline and Evodiamine decreased the level of E-selectin. All these changes were significant. Taken together, the data suggested that six alkaloids may effectively reduce inflammatory response via these cytokines.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Benzylisoquinolines; Cells, Cultured; Down-Regulation; Drugs, Chinese Herbal; E-Selectin; Endothelin-1; Endothelium, Vascular; Evodia; Humans; Interleukin-1alpha; Lipopolysaccharides; Morphinans; Proline; Pyrazines; Quinazolines; Quinolizines; Swine; Thromboxane B2