Scheidt C, Santos A R S, Ferreira J, Malheiros A, Cechinel-Filho V, Yunes R A, Calixto J B
Department of Pharmacology, Center of Biological Sciences, UFSC, Florianópolis, SC, Brazil.
Neuropharmacology. 2002 Sep;43(3):340-7. doi: 10.1016/s0028-3908(02)00117-x.
Drimanial, a new sesquiterpene isolated from the barks of the plant Drimys winteri (Winteraceae), given systemically, intraplantarly, or by spinal or supraspinal routes, produced pronounced antinociception against both phases of formalin-induced licking. The systemic injection of drimanial also inhibited, in a graded manner, the pain-related behaviours induced by intraplantar or intrathecal (i.t.) administration of glutamate. Moreover, drimanial also caused marked inhibition of the nociception induced by i.t. administration of a metabotropic glutamate agonist (1S,3R)-ACPD, without affecting nociceptive responses induced by ionotropic agonists (NMDA, kainate, AMPA) or by substance P. The antinociception caused by drimanial was not influenced by naloxone, nor did it interfere with the motor coordination of animals in the rota-rod test. Furthermore, drimanial caused graded inhibition of [(3)H]glutamate binding in cerebral cortical membranes from mice, with an IC(50) value of 4.39 micro M. Together, these results provide strong evidence indicating that the sesquiterpene drimanial produces antinociception in mice at peripheral, spinal and supraspinal sites. An interaction with metabotropic glutamate receptors seems to contribute to the mechanisms underlying its antinociceptive action.
从冬木姜子（樟科）树皮中分离出的一种新的倍半萜——地马尼亚尔，经全身、足底内、脊髓或脊髓上途径给药后，对福尔马林诱导的舔舐两个阶段均产生明显的抗伤害感受作用。地马尼亚尔的全身注射还以分级方式抑制了足底内或鞘内注射谷氨酸所诱导的疼痛相关行为。此外，地马尼亚尔还显著抑制了鞘内注射代谢型谷氨酸受体激动剂（1S,3R）-ACPD所诱导的伤害感受，而不影响离子型激动剂（NMDA、海人藻酸、AMPA）或P物质所诱导的伤害感受反应。地马尼亚尔引起的抗伤害感受不受纳洛酮影响，在转棒试验中也不干扰动物的运动协调。此外，地马尼亚尔对小鼠大脑皮质膜中[³H]谷氨酸结合产生分级抑制，IC₅₀值为4.39 μM。总之，这些结果提供了有力证据，表明倍半萜地马尼亚尔在小鼠的外周、脊髓和脊髓上部位产生抗伤害感受作用。与代谢型谷氨酸受体的相互作用似乎有助于其抗伤害感受作用的潜在机制。
