Szallasi A, Bíró T, Modarres S, Garlaschelli L, Petersen M, Klusch A, Vidari G, Jonassohn M, De Rosa S, Sterner O, Blumberg P M, Krause J E
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Eur J Pharmacol. 1998 Aug 28;356(1):81-9. doi: 10.1016/s0014-2999(98)00514-7.
Selected naturally occurring unsaturated dialdehyde sesquiterpenes and related bioactive terpenoids were assayed for vanilloid-like activity. Out of the 25 compounds tested, eight inhibited completely the specific binding of [3H]resiniferatoxin by rat spinal cord membranes: binding affinities ranged from 0.6 microM for cinnamodial to 19.0 microM for hebelomic acid F. These values were comparable to the binding affinity of capsaicin (2.7 microM). With the exception of four ligands, compounds that inhibited resiniferatoxin binding to rat spinal cord membranes were also pungent on the human tongue where they showed cross-tachyphylaxis with capsaicin. As expected from their reactive nature, these compounds possess additional sites of action, as reflected in the complex behavior of the stimulation of calcium influx by cinnamodial and cinnamosmolide at high concentrations. This observation might explain the unexpectedly weak membrane depolarization by cinnamodial compared to capsaicin. We conclude that a range of sesquiterpene dialdehydes and related terpenoids, both pungent and non-pungent, may function as vanilloids. These compounds may represent a new chemical lead for the development of vanilloid drugs, structurally unrelated to either capsaicin or resiniferatoxin.
对选定的天然存在的不饱和二醛倍半萜及相关生物活性萜类化合物进行了类香草酸活性测定。在测试的25种化合物中，有8种完全抑制了大鼠脊髓膜对[3H]树脂毒素的特异性结合：结合亲和力范围从肉桂醛的0.6微摩尔到海伯洛酸F的19.0微摩尔。这些值与辣椒素的结合亲和力（2.7微摩尔）相当。除了四种配体之外，抑制树脂毒素与大鼠脊髓膜结合的化合物在人舌上也有辛辣味，并且与辣椒素表现出交叉快速耐受性。正如从它们的反应性质所预期的那样，这些化合物具有额外的作用位点，这在高浓度下肉桂醛和肉桂醇酯对钙内流刺激的复杂行为中得到体现。这一观察结果可能解释了与辣椒素相比，肉桂醛出人意料地弱的膜去极化现象。我们得出结论，一系列倍半萜二醛及相关萜类化合物，无论辛辣与否，都可能作为类香草酸发挥作用。这些化合物可能代表了开发与辣椒素或树脂毒素结构无关的类香草酸药物的新化学先导物。
