title: Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis, and possible involvement of the adenosine system.
abstract: Incarvillea sinensis is a Bignoniaceae plant used to treat rheumatism and relieve pain in traditional Chinese medicine. As a major component of I. sinensis, incarvillateine has shown analgesic activity in mice formalin tests. Using a series of animal models, this study further evaluated the effects of incarvillateine against acute, inflammatory, and neuropathic pain. Incarvillateine (10 or 20 mg/kg, i.p.) dose-dependently attenuated acetic acid-induced writhing, but did not affect thermal threshold in the hot plate test. In a Complete Freund's Adjuvant model, incarvillateine inhibited both thermal hyperalgesia and paw edema, and increased interleukin-1β levels. Additionally, incarvillateine attenuated mechanical allodynia induced by spared nerve injury or paclitaxel, whereas normal mechanical sensation was not affected. Incarvillateine did not affect locomotor activity and time on the rotarod at analgesic doses, and no tolerance was observed after 7 consecutive daily doses. Moreover, incarvillateine-induced antinociception was attenuated by theophylline, 1,3-dipropyl-8-cyclopentylxanthine, and 3,7-dimethyl-1-propargylxanthine, but not naloxone, indicating that the effects of incarvillateine on chronic pain were related to the adenosine system, but not opioid system. These results indicate that incarvillateine is a novel analgesic compound that is effective against inflammatory and neuropathic pain, and that its effects are associated with activation of the adenosine system.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Mei-Liang
authors.initials: ML
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Shou-Pu
authors.initials: SP
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Zhi-Tong
authors.initials: ZT
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Rui-Bin
authors.initials: RB
authors.lastname: Su
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yan-Xing
authors.initials: YX
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Ze-Hui
authors.initials: ZH
authors.lastname: Gong
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D029402:Bignoniaceae / Q000737:chemistry* / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005620:Freund's Adjuvant / Q000737:chemistry; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D017239:Paclitaxel / Q000633:toxicity; D010147:Pain Measurement / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000972:Antineoplastic Agents, Phytogenic; D053583:Interleukin-1beta; D039821:Monoterpenes; D014970:Xanthines; C400141:incarvillateine; C057837:3,7-dimethyl-1-propargylxanthine; D005620:Freund's Adjuvant; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000241:Adenosine; D013805:Theobromine; D017239:Paclitaxel